System and apparatus comprising a multisensor guidewire for use in interventional cardiology

ABSTRACT

A system and apparatus comprising a multisensor guidewire for use in interventional cardiology, e.g. for Transcatheter Valve Therapies (TVT), comprises a plurality of optical sensors for direct measurement of cardiovascular parameters, e.g. transvalvular blood pressure gradients and flow. A conventional outer coil contains a shaped core wire having a cross-section defining helical grooves extending along its length, which accommodate optical fibers and optical sensors within a diameter D core  of the core wire. Advantageously, the diameter and material of the core wire provides the guidewire with sufficient stiffness for use as a support guidewire for valve replacement, e.g. Transcatheter Aortic Valve Implantation (TAVI), while accommodating multiple sensors and optical fibers within a guidewire of outside diameter ≦0.89 mm. An optical connector couples the guidewire to a control system. Optionally, the guidewire includes a contact force sensor; a pre-formed tip; and/or a separable micro-connector for proximal mounting of over-the-guidewire components.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Continuation-in-Part of PCT International Application No. PCT/IB2015/055240, entitled “System and Apparatus Comprising a Multisensor Guidewire for Use in Interventional Cardiology”, filed Jul. 10, 2015, designating the United States, and claiming priority from U.S. Provisional patent application No. 62/023,891, entitled “System And Apparatus Comprising a Multisensor Support Guidewire for Use in Trans-Catheter Heart Valve Therapies”, filed Jul. 13, 2014 and from U.S. Provisional patent application No. 62/039,952, entitled “System And Apparatus Comprising a Multisensor Support Guidewire for Use in Trans-Catheter Heart Valve Therapies”, filed Aug. 21, 2014; all said applications are incorporated herein by reference in their entirety.

This application is related to U.S. patent application Ser. No. 14/354,624 which is a national stage entry of PCT International Application No. PCT/IB2012/055893, entitled “Apparatus, system and methods for measuring a blood pressure gradient”, filed Oct. 26, 2012, which claims priority from U.S. Provisional patent application No. 61/552,778 entitled “Apparatus, system and methods for measuring a blood pressure gradient”, filed Oct. 28, 2011 and from U.S. Provisional patent application No. 61/552,787 entitled “Fluid temperature and flow sensor apparatus and system for cardiovascular and other medical applications”, filed Oct. 28, 2011, all of which are incorporated herein by reference, in their entirety.

TECHNICAL FIELD

The present invention relates to a system and apparatus comprising a multisensor guidewire for use in interventional cardiology, e.g. for Transcatheter heart Valve Therapies (TVT), such as, for Trans-catheter Aortic Valve Implantation (TAVI) and for related diagnostic measurements.

BACKGROUND

If a heart valve is found to be malfunctioning because it is defective or diseased, minimally invasive methods are known for repair and replacement of the heart valve, by introduction of a catheter intravascularly into the heart to access the heart valve. Percutaneous procedures for minimally invasive transcatheter heart valve repair and replacement avoid the need for open heart surgery. These procedures may be referred to as Transcatheter Valve Therapies (TVT).

TVT for valve repair include, for example, procedures such as, balloon valvuloplasty to widen an aortic valve which is narrowed by stenosis, or insertion of a mitral clip to reduce regurgitation when a mitral valve fails to close properly. Alternatively, if the valve cannot be repaired, a prosthetic replacement valve may be introduced. Minimally invasive Transcatheter heart Valve Replacement (TVR) procedures, including, Transcatheter Aortic Valve Implantation (TAVI) and Transcatheter Mitral Valve Implantation (TMVI), have been developed over the last decade and have become more common procedures in recent years.

While there have been many recent advances in systems and apparatus for TVT and for related diagnostic procedures, interventional cardiologists who perform these procedures have identified the need for improved apparatus for use in TVT, including apparatus for heart valve replacement. They are also seeking improved diagnostic equipment that provides direct measurements, i.e. within the heart, of important hemodynamic cardiovascular parameters before, during and after TVT.

The above referenced related PCT application No. PCT/IB2012/055893 (Publication No. WO/2013/061281), having common inventorship and ownership with the present application, discloses a multisensor micro-catheter or guidewire which comprises a distal end portion containing multiple optical sensors arranged for measuring blood pressure at several sensor locations, simultaneously in real-time. It optionally includes a sensor for measuring blood flow. In particular, the multisensor micro-catheter or guidewire is designed for use in minimally invasive surgical procedures for measurement of intra-vascular pressure gradients, and more particularly, for direct measurement of a transvalvular pressure gradient within the heart.

To obtain accurate measurements of hemodynamic parameters such as blood pressure, blood flow, a blood pressure gradient, or other parameters within the heart, it is desirable that the sensor guidewire does not interfere with normal operation of the heart and the heart valves. Thus, beneficially, a fine diameter guidewire, e.g. ≦0.89 mm diameter, with a flexible tip, facilitates insertion through a heart valve without trauma, and reduces interference with valve operation. That is, when the sensor guidewire is inserted through the valve, it preferably causes minimal interference with the movement of the valve and/or does not significantly perturb the transvalvular pressure gradient or other parameters. For example, in use, a multisensor guidewire may be introduced via the aorta, through the aortic valve, and positioned so that the optical pressure sensors are located both upstream and downstream of the aortic valve, for direct measurement of the transvalvular blood pressure gradient, and optionally also blood flow, with minimal disruption of the normal operation of the aortic valve. Accordingly, a fine gauge guidewire minimizes disruption of the heart valve activity during measurement, to obtain accurate measurements of the transvalvular pressure gradient or other parameters.

A reliable measurement of a transvalvular pressure gradient through several cardiac cycles is an important parameter to assess whether the heart valve is functioning well or malfunctioning. An optical multisensor pressure sensing guidewire of this structure provides a valuable tool that an interventional cardiologist can use to facilitate direct measurements of cardiovascular parameters, including a transvalvular pressure gradient. Such measurements provide information relating to parameters, such as, an aortic regurgitation index, stenotic valve orifice area and cardiac output.

As described in the above referenced related patent applications, typically, a conventional support guidewire used for a transcatheter valve replacement procedure, such as TAVI, comprises an outer tubular layer in the form of a flexible metal coil, and a central metal core wire or mandrel to provide stiffness and torque characteristics. The outer metal coil and inner core wire act together to provide a suitable combination of flexibility and stiffness, which, together with a suitably shaped tip, allow the guidewire to be directed or guided through the blood vessels, i.e. intravascularly, into the heart.

In the multisensor guidewire disclosed in the above referenced PCT International Application No. PCT/IB2012/055893, the optical sensors, e.g. 3 or 4 optical pressure sensors, are located in a distal end portion of the sensor guidewire, and coupled by respective individual optical fibers to an optical input/output at the proximal end of the guidewire. It will be appreciated that to fit a plurality of optical sensors and optical fibers within a guidewire comprising a small gauge outer coil, e.g. ≦0.89 mm (0.035 inch), the diameter of core wire is made as small as possible, i.e. to allow sufficient space around the core wire to accommodate the optical fibers and sensors between the core wire and the coil. For example, standard optical fibers have a diameter of 0.155 mm, which would require a core wire having a diameter of only 0.5 mm for a 0.89 mm outside diameter guidewire. Since the stiffness of a wire varies as the fourth power of its diameter, the small diameter core wire significantly reduces the stiffness of the multisensor guidewire. That is, the optical fibers and sensors take up space within the micro-catheter or guidewire coil but do not contribute significantly to the stiffness.

In testing of prototype multisensor guidewires, it has been found that the strong blood flow and turbulence within the heart can be sufficient to displace a small-gauge flexible guidewire, and tends to push the guidewire back into the aorta. Thus, during measurement of a transvalvular pressure gradient, movement of the guidewire may create difficulty in positioning the sensors and the cardiologist may need to readjust the positioning of the guidewire to maintain the pressure sensors each side of the heart valve. On the other hand, in a multisensor guidewire of this structure, to accommodate a plurality of optical sensors and respective optical fibers around a larger diameter stiffer core wire would require a larger outside diameter outer coil, i.e. larger than 0.89 mm. While a larger gauge, stiffer guidewire would be less easily displaced during measurements, for measurement of transvalvular pressure gradients, it would tend to interfere more with normal heart valve operation, and may increase the risk of tissue damage. Accordingly, a need for further improvements has been identified.

If diagnostic measurements of hemodynamic/cardiac parameters indicate the need for valve replacement, minimally invasive transcatheter valve replacement procedures, such as TAVI, can be performed to insert a replacement or prosthetic valve, e.g. comprising leaflets made of biologic tissue supported within an expandable metal frame.

Examples of current prosthetic valves and valve delivery systems are illustrated and described and illustrated in an article entitled “Current Status of Transcatheter Aortic Valve Replacement”, by John G. Webb, MD, David A. Wood, MD, Vancouver, British Columbia, Canada; Journal of the American College of Cardiology, Vol. 60, No. 6, 2012.

Very briefly, the TAVI procedure requires that a support guidewire, which is a relatively stiff guidewire (TAVI guidewire) with a flexible tip, is introduced into the heart and through the aortic valve. For example, the interventional cardiologist introduces the support guidewire through a catheter inserted into the femoral artery, i.e. in the groin, and moves it up through the aorta into the heart. The tip of the TAVI guidewire is introduced into the aorta, through the malfunctioning aortic valve, and into the left ventricle of the heart. Once the support guidewire is anchored within the ventricle, a delivery device holding the replacement valve is passed over the support guidewire. The cardiologist guides the delivery device carrying the replacement valve over the support guidewire and manoeuvres the valve into position within the aortic valve. The replacement valve is expanded, so that the patient's malfunctioning aortic valve is pushed out of the way. The valve frame may be self-expandable or balloon-expandable, depending on the valve type and the delivery system. Once expanded, the metal frame engages the wall of the aorta and holds the replacement valve in position. When the delivery system is withdrawn, the leaflets on the replacement valve are able to unfold and then function in a manner similar to the leaflets of the natural aortic valve.

Commercial availability of an optical multisensor guidewire or multisensor micro-catheter as described in the above referenced related U.S. patent application Ser. No. 14/354,624, (now issued to U.S. Pat. No. 9,149,230), would provide the interventional cardiologist with a useful tool for directly measuring a pressure gradient before and after such a procedure for valve repair or replacement, e.g. for TAVI. For example, it is envisaged that the interventional cardiologist would introduce the fine gauge multisensor guidewire to measure a transvalvular pressure gradient, and optionally blood flow, to assess pre-implantation functioning of the heart and the damaged or malfunctioning aortic valve. After withdrawing the multisensor guidewire, the cardiologist would perform a transcatheter heart aortic valve implantation procedure using a specialized, more robust and stiffer support guidewire (TAVI guidewire) to deliver the valve implant into the heart and perform the implantation. Subsequently, after completing the TAVI procedure, the TAVI guidewire would be withdrawn. The multisensor guidewire would then be reintroduced to measure a transvalvular pressure gradient and flow, to assess post-implant functioning of the replacement valve.

For TAVI, a relatively stiff support guidewire, typically 0.035 inch (0.89 mm) in diameter, is required. For example, guidewire manufacturers may use a descriptive term, such as, “stiff” or “super stiff” to provide an indication of the guidewire stiffness. Based on experience, an interventional cardiologist will select a guidewire with an appropriate stiffness and/or other mechanical characteristics to suit a particular transcatheter valve replacement procedure. Such a description of stiffness or flexibility can be related in mechanics to a measurement of a flexural modulus, which is a ratio of stress to strain in flexural deformation, or, what may be described as the tendency for a material to bend.

During a TAVI procedure, the support guidewire must be firmly anchored within the left ventricle for insertion of the valve delivery system and so that the replacement valve can be accurately positioned and held firmly in place while it is expanded. When a stiff support guidewire is introduced into the left ventricle of the heart through the aortic valve, if too much force is applied to the guidewire or it is pushed too far, there is some risk that the guidewire could cause damage or trauma to the heart tissues, e.g. damage to the aortic wall or ventricular perforation and pericardial effusion resulting in pericardial tamponade. Moreover, there is increased risk of trauma or damage to the heart wall in a diseased, weakened or calcified heart. To reduce risk of trauma or ventricular perforation, typically the tip of the support guidewire is relative soft and flexible. It may be pre-formed as a J-tip or it may be resiliently deformable so that it can be manually shaped as required by the cardiologist. Recently, specialized TAVI guidewires have become commercially available with pre-formed curved tips of other forms. For example, the Boston Scientific Safari™ pre-shaped TAVI guidewire has a double curve tip, and the Medtronic Confida™ Brecker Curve™ guidewire has a spiral tip. Reference is also made, by way of example, to structures described in US patent publication No. US2012/0016342 and PCT Publication No. WO2010/092347, each to Brecker, entitled “Percutaneous Guidewire”; PCT Publication No. WO2014/081942, to Mathews et al., entitled “Preformed Guidewire”; and PCT Publication No. 2004/018031 to Cook, entitled “Guidewire”. See also, an article by D. A. Roy et al., entitled “First-in-man assessment of a dedicated guidewire for transcatheter aortic valve implantation”, EuroIntervention 2013; 8, pp. 1019-1025.

While significant advances have recently been made, interventional cardiologists have identified a need for further improvements or alternatives to available guidewires and diagnostic tools for use in minimally invasive intravascular procedures and cardiac interventions, such as TAVI, or other TVT. In particular, it is desirable to have improved apparatus to simplify or facilitate transcatheter valve replacement procedures, including apparatus that will assist in reducing the risk of tissue trauma, e.g. damage to the aorta, the valve or the ventricular wall when much force is exerted on the support guidewire. Additionally, improved systems and apparatus that would provide for direct (in situ) diagnostic measurements within the heart, before, during and after at least some TVT procedures would potentially assist in understanding factors that contribute to successful outcomes and/or issues that may contribute to mortality or need for re-intervention.

Thus, an object of the present invention is to provide for improvements or alternatives to multisensor guidewires, including support guidewires for transcatheter valve replacement procedures and/or to multisensor diagnostic guidewires that enable direct measurements of cardiovascular parameters at multiple locations within the heart, such as, measurement of a transvalvular pressure gradient.

SUMMARY OF INVENTION

The present invention seeks to mitigate one or more disadvantages of known systems and apparatus for measuring cardiovascular parameters, and/or for performing interventional cardiac procedures, including transcatheter valve therapies (TVT), for heart valve repair and/or replacement.

A first aspect of the invention provides a multisensor guidewire for measuring blood pressure concurrently at multiple locations during a minimally invasive intravascular or cardiac intervention, comprising:

a tubular covering layer comprising an outer flexible coil, the coil having a length extending between a proximal end and a distal end, an outside diameter of ≦1 mm, a core wire extending within the coil from the proximal end to the distal end, and the distal end comprising a flexible distal tip; a plurality of optical sensors and a plurality of optical fibers; a sensor end of each optical fiber being attached and optically coupled to an individual one of the plurality of optical sensors; the core wire having an external surface with a cross-sectional profile defining a plurality of grooves extending along a length of the core wire, each groove accommodating an individual optical fiber and a respective optical sensor within a diameter D_(core) of the core wire and providing a sensor arrangement with said plurality of optical sensors positioned at respective sensor locations within a distal end portion of the guidewire; a proximal end of each of the plurality of optical fibers being coupled to an optical input/output connector at the proximal end of the guidewire for connection to an optical control system; and the plurality of optical sensors of the sensor arrangement including at least two optical pressure sensors at respective sensor locations spaced apart lengthwise along a length of said distal end portion.

Thus, a specially shaped core wire is provided which is grooved to accommodate and position the optical fibers and their respective sensors with the diameter D_(core) of the core wire.

In embodiments comprising a multisensor support guidewire, the grooved core wire accommodates a plurality of optical fibers within a standard diameter multisensor guidewire with a core wire of a diameter D_(core) that provides a required stiffness, typical of a support guidewire for transcatheter valve replacement.

The plurality of optical fibers and optical sensors sit within the grooves formed in the surface of the core wire, and the grooves preferably have a depth that is sufficient that the fibers and sensors are accommodated completely within the grooves and within a diameter D_(core) of the core wire. The fibers and sensors are thereby protected within the grooves, during assembly and in use of the guidewire.

If required, e.g. if the sensors are of larger diameter than the optical fibers, at sensor positions in the distal end portion, recesses or cavities may be formed in the core wire at sensor locations to accommodate the optical sensors, e.g. by enlarging the grooves at sensor locations. The cavities optionally include radiopaque markers adjacent each sensor for locating the sensors in use, e.g., by conventional radio-imaging techniques.

Beneficially, the grooves are symmetrically spaced around the core wire. That is, the core wire preferably has rotational symmetry, e.g. three-fold or four-fold symmetry, with a corresponding plurality of three or four grooves spaced symmetrically around the circumference of the core wire. This provides rotationally symmetric stiffness and torque characteristics to the core wire for flexing and steering the guidewire. Preferably the grooves have some rotation around the core wire, e.g. they are helical grooves. For example, the helical grooves have a pitch of at least 25 mm (1 inch). Accordingly, a multisensor guidewire is provided with a helically grooved core wire that can accommodate multiple fibers and optical sensors while optimizing the stiffness and torque characteristics of the multisensor guidewire comprising a core wire of a particular diameter D_(core).

The core wire may be formed by wire-drawing, from a medical grade metal alloy, such as stainless steel. In this case, surfaces of the core wire defining the grooves are radiused to no less than a minimum radius R_(min) to enable fabrication of the grooves by a wire-drawing process.

Each optical fiber may be adhesively bonded to the core wire at least at one point, e.g. within its respective groove at a point adjacent the sensor location and optionally also at the proximal end of the core wire.

The coil preferably has an outside diameter of ≦0.89 mm (≦0.035 inch). The outer coil and the optical fibers do not contribute significantly to the stiffness of the guidewire. Thus, the stiffness of the guidewire is primarily determined by the material and the diameter of the core wire. The material and diameter D_(core) of the core wire, in at least the distal end portion, provides a flexural modulus of a predetermined stiffness to the guidewire.

Typically, the guidewire stiffness is described by guidewire manufacturers using standard guidewire descriptors such as “stiff” or “super stiff”.

For example, when the multisensor guidewire is for use as a support guidewire for TVR, the core wire may comprise a medical grade stainless steel alloy and the diameter D_(core) of the core wire provides the guidewire with predetermined stiffness characteristics, such as, defined by a standard guidewire descriptor, said guidewire descriptor being one of stiff, super-stiff and ultra-stiff.

In some embodiments, the core wire comprises a medical grade stainless steel alloy and the diameter D_(core) of the core wire in at least the distal end portion provides a flexural modulus of 60 GPa+/−10%. In some embodiments, the core wire comprises a medical grade stainless steel alloy and the diameter D_(core) of the core wire in at least the distal end portion provides a flexural modulus of 60 GPa or more.

In an embodiment, the multisensor guidewire is configured measuring a transvalvular blood pressure gradient within the heart during a minimally invasive cardiac intervention, wherein said plurality of optical sensors comprise Fabry-Pérot MOMS pressure sensors and said sensor locations are spaced apart lengthwise along said length of the distal end portion to provide for one or more of:

a) placement of at least one pressure sensor in the aorta downstream of the aortic valve and placement of at least one pressure sensor in the left ventricle, upstream of the aortic valve for measurement of a transvalvular blood pressure gradient for the aortic valve; b) placement of at least one pressure sensor in the left atrium upstream of the mitral valve and placement of at least one pressure sensor in the left ventricle, downstream of the mitral valve for measurement of a transvalvular blood pressure gradient for the mitral valve; c) placement of at least one pressure sensor in the right atrium upstream of the tricuspid valve and placement of at least one pressure sensor in the right ventricle, downstream of the tricuspid valve, for measurement of a transvalvular blood pressure gradient for the triscuspid valve; and d) placement of at least one pressure sensor in the right ventricle upstream of the pulmonary valve and placement of at least one pressure sensor in the pulmonary artery, downstream of the pulmonary valve for measurement of a transvalvular blood pressure gradient for the pulmonary valve.

Thus, the plurality of optical sensors, including two or more optical pressure sensors at sensor locations spaced apart along a length of the distal end portion of the core wire, are positioned for placement upstream and downstream of a heart valve for measuring pressure at a plurality of sensor locations, concurrently, to provide a transvalvular pressure gradient.

Optionally, the plurality of optical sensors further comprises an optical flow sensor for monitoring blood flow in addition to measurement of blood pressure and blood pressure gradients, e.g. to enable computation of the valve area. In one embodiment, the optical flow sensor is positioned proximally of the pressure sensors, i.e. to measure blood flow in the ascending aorta downstream of the aortic valve and before the branches from the aorta, e.g. about 50 mm to 80 mm from the aortic valve or a distance L_(FS) of about 20 mm upstream from the most proximal optical pressure sensor. Multisensor guidewires of alternative embodiments, comprising other spacings of two or more pressure sensors and a flow sensor, are also disclosed.

In a multisensor guidewire of an embodiment for use as a support guidewire for TVR, the multisensor guidewire comprises three or four optical sensors and respective optical fibers, wherein the distal end portion of the coil has an external diameter ≦0.89 mm (≦0.035 inch), and the core wire provides a guidewire having a flexural modulus of 60 GPa or more. The optical sensors comprise for example two optical pressure sensors and optionally, an optical flow sensor.

Where required, apertures are provided in the coil adjacent each optical pressure sensor for fluid contact therewith, and radiopaque markers are provided adjacent each optical pressure sensor.

Where the multisensor guidewire is to be used as a support guidewire for transcatheter valve replacement, to enable over-the-wire delivery of components, the multisensor guidewire may comprise separable distal and proximal parts connected by a micro-optical coupler. The multisensor guidewire forms the distal part and the proximal part comprises a flexible optical coupling to the control system. Thus, the distal part comprises a male connector of the optical coupler and the proximal part comprises a female connector of the optical coupler, the male connector having an outside diameter no greater than the outside diameter of the coil of the guidewire. For example, a proximal end of the core wire comprises a tapered portion that extends to form a core of the male connector and the plurality of optical fibers emerge from the grooves and extend around the tapered portion, around the core, and through a surrounding body or ferrule of the male connector which has an outside diameter of no greater than 0.89 mm. Preferably, the micro-optical coupler comprises alignment means and/or fastening means to facilitate quick connection/re-connection, with optical alignment of the multiple optical fibers, and to securely lock together the proximal and distal parts of the guidewire apparatus.

In an embodiment, the multisensor guidewire comprises separable distal and proximal parts connected by an optical coupler, said optical coupler securely fastening together the distal and proximal part, with optical alignment and coupling of the individual ones of the plurality of optical fibers of the distal part to corresponding individual ones of a plurality of optical fibers of the proximal part, and the proximal part being more flexible than the distal part for optically coupling the distal part to the control system.

In another embodiment, the multisensor guidewire comprises separable distal and proximal parts, and further comprising a separable micro-optical coupler comprising a female connector and a male connector coupling the proximal and distal parts, the distal part carrying the male connector, and the male connector having a diameter no greater than the outside diameter of the coil, to enable proximal mounting of components on/over-the-guidewire.

Optionally, the plurality of optical sensors further comprises an optical contact force sensor adjacent to, or within, the distal tip, the optical contact force sensor being configured for sensing a force applied by the distal end portion of the guidewire to surrounding tissue. A system comprising a sensor guidewire with a contact force sensor allows for a control system to monitor the contact force applied to said length of the distal end portion and provides feedback indicative of the contact force.

The contact force sensor monitors a contact force applied to a length of the distal end portion of the guidewire, e.g. to provide feedback to the interventional cardiologist when a threshold contact force is reached and to assist in avoiding tissue trauma or perforation. The system may provide an alert when the contact force exceeds a predetermined threshold value, e.g. during insertion of the support guidewire into the left ventricle for TAVI, to assist the cardiologist in avoiding tissue trauma.

In some embodiments, to accommodate a plurality of optical sensors within a guidewire of diameter ≦0.89 mm (≦0.035 inch) and with a core wire providing a required stiffness, the number sensors may be limited to a maximum of two, three or four sensors. For example, for some applications, if only three sensors can be accommodated, it may be preferred to provide two optical pressure sensors and one flow sensor to enable measurements of a transvalvular pressure gradient and blood flow. If a fourth sensor can be accommodated, while still providing sufficient stiffness, it may be another pressure sensor, or a contact force sensor.

Beneficially, to assist in anchoring of the guidewire during TVR, e.g. anchoring the guidewire within the left ventricle for TAVI, the flexible distal tip comprises an atraumatic tip such as a J-tip or other pre-formed curved tip. The flexible distal tip may comprise a pre-formed atraumatic tip, for example, comprising one of: a J-tip, spiral or another two dimensional curved shape; a three dimensional curved form; a helical structure, e.g. resembling a pigtail or phone cord; and a tapered helical structure, e.g. resembling the form of a snail shell.

Another aspect of the invention provides a core wire for a multisensor guidewire, wherein the multisensor guidewire has an outer flexible coil having an external diameter of ≦1 mm and the guidewire contains a plurality of optical sensors and a corresponding plurality of optical fibers, the core wire being fabricated from a medical grade metal alloy and having a diameter D_(core), an external surface of the core wire defining a plurality of grooves extending along the length of the guidewire, each groove having a depth that can accommodate an individual one of said plurality of optical fibers within the diameter D_(core) of the core wire, and wherein D_(core) is sized to fit slideably with the outer flexible coil of a guidewire.

Preferably, the plurality of grooves have some rotation around the core wire, e.g. extend helically along the length of the core wire, and the plurality of grooves are spaced symmetrically around the core wire.

For a multisensor guidewire with high stiffness, e.g. for use as a support guidewire, the core wire comprises a medical grade stainless steel alloy, such as 304V. To facilitate formation of the grooves by wire-drawing, radiused surfaces of the grooves have at least a minimum radius required for wire drawing.

Another aspect of the invention provides a method of assembly of a multisensor guidewire including a flexible outer coil and a core wire extending therethrough, the method comprising: providing a core wire having an external surface and cross-sectional profile defining a plurality of grooves defined along its length; providing a plurality of optical fibers, each optical fiber having at its distal end an optical sensor; attaching the optical fibers and their respective optical sensors to the core wire to form a sub-assembly with optical sensors spaced apart lengthwise along a distal end portion of the core wire, and with each optical fiber and its respective sensor sitting within a respective groove of the core wire; and inserting the sub-assembly into the outer coil of the guidewire.

Thus, apparatus and systems comprising a multisensor guidewire are provided that mitigate one or more problems with known systems and apparatus for TVT. In particular, some embodiments provide a multisensor support guidewire, with high stiffness, which can be used for minimally invasive transcatheter valve replacement procedures and which also provides for direct measurement of hemodynamic parameters, such as intravascular or transvalvular pressure gradients and flow, before and after the valve replacement. In other embodiments more flexible multisensor guidewires are provided for other percutaneous, minimally invasive intravascular procedures, comprising diagnostic measurements of hemodynamic parameters including blood pressure gradients.

Also provided is a grooved core wire which can provide high stiffness for multisensor support guidewires, and methods of fabrication of multisensor guidewires with improved stiffness and torque characteristics.

The foregoing and other objects, features, aspects and advantages of the present invention will become more apparent from the following detailed description, taken in conjunction with the accompanying drawings, of embodiments of the invention, which description is by way of example only.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, identical or corresponding elements in the different Figures have the same reference numeral.

FIG. 1 illustrates schematically a system according to a first embodiment, comprising a multisensor guidewire apparatus optically coupled to a control unit;

FIG. 2 illustrates schematically a longitudinal cross-sectional view of an apparatus comprising a multisensor support guidewire comprising a plurality of optical sensors according to a first embodiment of the present invention;

FIG. 3 illustrates schematically an enlarged longitudinal cross-sectional view showing details of the distal end portion of the multisensor guidewire illustrated in FIG. 2;

FIGS. 4A, 4B, 4C and 4D show enlarged axial cross-sectional views of the multisensor guidewire illustrated in FIG. 2 taken through planes A-A, B-B, C-C and D-D respectively;

FIG. 5 illustrates schematically a longitudinal cross-sectional view of an apparatus comprising a multisensor guidewire comprising a plurality of optical sensors according to another embodiment of the present invention;

FIG. 6A illustrates schematically an enlarged longitudinal cross-sectional view showing details of the distal end portion of the multisensor guidewire illustrated in FIG. 5; and FIG. 6B shows an enlarged and simplified cross-sectional view along the axis of a groove, such as through plane X-X of FIG. 6A;

FIGS. 7A, 7B, 7C, 7D and 7E show enlarged axial cross-sectional views of the multisensor guidewire illustrated in FIG. 5 taken through planes A-A, B-B, C-C D-D and E-E respectively;

FIGS. 8A, 8B, 8C, 8D and 8E show enlarged axial cross-sectional views of the multisensor guidewire similar to those shown in FIGS. 7A to 7E, for an embodiment comprising fibers and grooves of different dimensions;

FIG. 9 shows an enlarged axial cross-sectional view of a core wire of another embodiment;

FIGS. 10A and 10B, show enlarged axial cross-sectional views of core wires of other embodiments;

FIG. 11A shows a schematic diagram of a human heart to illustrate placement within the left ventricle of a multisensor guidewire, similar to that shown in FIG. 2, for use as: a) a guidewire during a TAVI procedure; and b) for directly measuring a blood pressure gradient across the aortic heart valve before and after the TAVI procedure;

FIG. 11B shows a schematic diagram of a human heart to illustrate placement within the left ventricle of a multisensor guidewire, similar to that shown in FIG. 5, for use as: a) a guidewire during a TAVI procedure; and b) for directly measuring a blood pressure gradient across the aortic heart valve before and after the TAVI procedure, wherein a flow sensor is provided for measuring blood flow upstream of the aortic valve;

FIGS. 12A, 12B and 12C show corresponding schematics of a human heart illustrating three potential approached for placement of the multisensor guidewire through the mitral valve, for use as: a) a support guidewire during a transcatheter valve replacement procedure; and b) as a diagnostic tool for directly measuring a blood pressure gradient across the heart valve before and after the transcatheter valve replacement procedure;

FIG. 13 shows a corresponding schematic of a human heart illustrating placement of the multisensor guidewire through the tricuspid valve, for use as: a) a support guidewire during a transcatheter valve replacement procedure; and b) for directly measuring a blood pressure gradient across the heart valve before and after the transcatheter valve replacement procedure;

FIG. 14 shows a corresponding schematic of a human heart illustrating placement of the multisensor guidewire through the pulmonary valve, for use as: a) a support guidewire during a transcatheter valve replacement procedure; and b) for directly measuring a blood pressure gradient across the heart valve before and after the transcatheter valve replacement procedure;

FIG. 15 shows a chart, known as a Wiggers diagram, showing typical cardiac blood flow and pressure curves during several heart cycles, for a healthy heart;

FIGS. 16A, 16B and 16C show simplified schematics representing the aortic heart valve and left ventricle in a healthy heart, with the multisensor guidewire inserted through the aortic valve with first and second optical pressure sensors P1 and P2 positioned within the ventricle and the third optical pressure sensor P3 positioned within the aorta for measurement of a transvalvular pressure gradient through the aortic valve in a healthy heart, with the heart valve in closed, semi-closed/open and open positions respectively;

FIGS. 17A, 17B and 17C show similar simplified schematics representing the aortic heart valve and left ventricle, in which shaded areas represent stenoses, with the multisensor guidewire inserted through the aortic valve with first and second optical pressure sensors P1 and P2 positioned within the ventricle and the third optical pressure sensor P3 positioned within the aorta for measurement of a transvalvular pressure gradient through the aortic valve in a diseased heart, with the heart valve in closed, semi-closed/open and open positions respectively;

FIG. 18 shows a chart showing typical variations to the blood flow or pressure curves, during several cardiac cycles, due to cardiac stenosis;

FIG. 19 illustrates schematically a view of the male and female connectors of the micro-optical coupler for optically coupling the distal and proximal parts of the multisensor guidewire;

FIG. 20 illustrates schematically an enlarged longitudinal cross-sectional view of the male part of the multisensor guidewire optical connector illustrated in FIG. 19;

FIGS. 21A, 21B, 21C and 21D show enlarged axial cross-sectional views of the multisensor guidewire optical connector illustrated in FIG. 20 taken, respectively, through planes A-A, B-B, C-C and D-D indicated in FIG. 20;

FIG. 22 illustrates schematically a side perspective view an optical contact force sensor (strain gauge) for use in a multisensor guidewire for cardiovascular use such as for TVR;

FIG. 23 illustrates a longitudinal cross-sectional view of the optical contact force sensor (strain gauge) of FIG. 22;

FIG. 24 illustrates schematically a longitudinal cross-sectional view showing details of the distal end portion of a multisensor guidewire of a third embodiment comprising a contact force sensor such as illustrated in FIG. 22;

FIGS. 25A and 25B show enlarged axial cross-sectional views of the multisensor guidewire comprising a contact force sensor illustrated in FIG. 23 taken, respectively, through planes A-A and B-B indicated in FIG. 24;

FIG. 26 shows a schematic diagram of a human heart to illustrate placement within the left ventricle of a multisensor guidewire, similar to that shown in FIG. 23, for sensing a contact force, e.g. during a TAVI procedure or during measurement of cardiovascular parameters before, during and after the TAVI procedure;

FIGS. 27A and 27B, show enlarged views of the distal end of a guidewire wherein the tip comprises pre-formed helical tip of a first embodiment;

FIG. 28 shows a schematic diagram of a human heart to illustrate placement of within the left ventricle of a guidewire comprising a flexible pre-formed helical tip as shown in FIGS. 27A and 27B;

FIGS. 29A and 29B show enlarged views of views of the distal end of a guidewire wherein the tip comprises a pre-formed helical tip of another embodiment; and

FIG. 30 shows a schematic diagram of a human heart to illustrate placement within the left ventricle of a multisensor support guidewire, comprising a pre-formed helical tip as shown in FIGS. 29A and 29B.

DETAILED DESCRIPTION OF EMBODIMENTS

A system and apparatus comprising a multisensor guidewire for use in interventional cardiology, which may include diagnostic measurements of cardiovascular parameters and/or transcatheter valve replacement or repair, according to an embodiment of the present invention will be illustrated and described, by way of example, with reference to a system comprising a support guidewire for use in a TAVI procedure, for aortic valve replacement.

Firstly, referring to FIG. 1, this schematic represents a system 1 comprising an apparatus 100 comprising a multisensor guidewire for use in transcatheter valve replacement procedures, coupled to a control system 150, which houses a control unit 151 and user interface, such as the illustrated touch screen display 152. The apparatus 100 comprises a proximal part 101 and distal part 102. The distal part 102 takes the form of a multisensor guidewire and comprises components of a conventional guidewire comprising a tubular outer layer in the form of a flexible fine metal coil 35 and an inner mandrel or core wire 31 within the outer coil 35. The outer coil 35 and the core wire 31 each have a diameter and mechanical properties to provide the required stiffness to act as a “support guidewire” for TAVI, i.e. for over-the-wire delivery of a replacement valve. Typically, for TAVI, the coil has an outside diameter of 0.035 inch (0.89 mm) or less, the guidewire has a suitable stiffness for transcatheter or intra-vascular insertion, and extends to distal tip 120, such as a flexible J-tip, or other atraumatic curved tip, to facilitate insertion. By way of example, a guidewire for transcatheter valve replacement may typically be about 2 m to 3 m in length, e.g. 2.6 m.

To provide the appropriate stiffness and other mechanical properties, coil 35 and core wire 31 are typically stainless steel, although other suitable medical grade metals or alloys may alternatively be used. The distal part 102 differs from a conventional guidewire in that, internally, it also contains a sensor arrangement 130 comprising a plurality of optical sensors (not visible in FIG. 1), located within the distal end portion 103, near the distal tip 120. For example, as will be described in detail with reference to FIG. 2 and FIG. 3, three optical pressure sensors 10 a, 10 b and 10 c are provided in a length L of the distal end portion 103 spaced by distances L₁ and L₂. Optionally, as illustrated in FIG. 2, the sensor arrangement also includes an optical flow sensor 20, e.g., positioned proximally of the flow sensors by a distance L_(FS). Thus, internally, the distal part 102 provides optical coupling of the optical sensors 10 a, 10 b, 10 c and 20, through a plurality of optical fibers 11, to an optical coupler 140 at its proximal end, as will also be described in detail with reference to FIGS. 2, 3, 4A, 4B, 4C and 4D.

The proximal part 101 of the apparatus 100 provides for optical coupling of the distal part 102 to the control unit 151. The proximal part 101 has at its proximal end 110 an optical input/output 112, such as a standard type of optical fiber connector which connects to a corresponding optical input/output connector 153 of the control unit 151. Thus, the proximal part 101 is effectively an elongate, flexible optical coupler, e.g. a tubular flexible member containing a plurality of optical fibers, with the optical coupler 140 at its distal end for optical coupling of the distal part 102, i.e. the multisensor guidewire. The control unit 151 houses a control system comprising a controller with appropriate functionality, e.g. including a processor, data storage, and optical source and optical detector, and it provides a user interface, e.g. a keypad 154, and touch screen display 152, suitable for tactile user input, and for graphical display of sensor data. The user interface cable 155 (e.g. a standard USB cable) is used to transfer data between the control unit 151 to the touch screen display 152. The control unit 151 and touch screen display 152 may optionally be integrated within a single housing or module.

The internal structure of the multisensor guidewire apparatus 100 will now be described in more detail with reference to FIGS. 2 and 3.

FIG. 2 illustrates schematically a longitudinal cross-sectional view of the apparatus 100 according to the first embodiment of the invention, comprising a multisensor guidewire. The apparatus 100 extends from the optical input/output connector 112 at the proximal end 110 through the proximal part 101 to the distal part 102 which extends to the distal tip 120.

The distal part 102 takes the form of a multisensor guidewire and comprises components of a conventional guidewire comprising a tubular outer layer in the form of a flexible fine metal coil 35 and an inner mandrel or core wire 31 within the outer coil 35. The outer coil 35 and the core wire 31 each have a diameter and mechanical properties to provide the required flexibility and stiffness to act as a support guidewire for TAVI. Typically, for TAVI, the coil forms a flexible tubular covering layer of the guidewire and has an outside diameter of 0.035 inch or 0.89 mm or less. To provide the appropriate stiffness and other mechanical properties, such as torque characteristics, for a support guidewire, coil 35 and core wire 31, are typically stainless steel, although other suitable metals or alloys may alternatively be used. As illustrated schematically in FIG. 2, in this embodiment, the coil wire is formed from a flat ribbon wire having a rectangular cross-section. If required, the outer coil of guidewire may comprise a coating of a suitable biocompatible material, e.g. to facilitate insertion and steering control. The coating may be a hydrophobic coating, such as PTFE or silicone, or a hydrophilic material. For example, in some instances, the guidewire has a hydrophobic coating along its length and the distal end portion and distal tip has a hydrophilic coating.

In this embodiment, the sensor arrangement 130 comprises a plurality of optical sensors, i.e. three optical pressure sensors 10 a, 10 b, 10 c arranged along a length L of a distal end portion 103 near the distal tip 120, for measuring pressure concurrently at each sensor location. Each of the optical pressure sensors is attached and optically coupled to a sensor end (i.e. a distal end) of a respective individual optical fiber 11. That is each optical fiber carries an individual sensor, e.g. bonded to the sensor end of the fiber or integrally formed therewith. Optionally, another type of optical sensor, e.g. an optical flow sensor 20 as mentioned above, may be provided in or near the distal end portion 103, and coupled to another respective optical fiber 11.

For example, for measuring a transaortic pressure gradient, the optical pressure sensors 10 a, 10 b, 10 c are arranged spaced apart by distances L₁ and L₂, e.g. 20 mm and 50 mm to 60 mm respectively, for placement of the sensors upstream and downstream of the aortic valve. Optionally, a flow sensor 20 (see FIGS. 2 and 5B) is positioned to measure flow in the aorta before the main branches from the aorta, e.g. in the ascending aorta, about 50 mm to 80 mm downstream of the aortic valve 511 or a distance L_(FS) of about 20 mm from the nearest pressure sensor 10 b or 10 c (see FIGS. 2, 5B, 11A and 11B).

FIG. 3 shows an enlarged longitudinal cross-sectional view of the distal end portion 103 of the multisensor guidewire 100 illustrated in FIG. 2. As illustrated, in FIG. 2 and FIG. 3, to accommodate the plurality of optical sensors 10 a, 10 b, 10 c and 20 and their respective optical fibers 11 while maintaining the required stiffness to the guidewire, the core wire is provided with a corresponding plurality of helical grooves 32. The helical grooves 32 extend along the length of the core wire 31 from the optical coupler 140 to near the distal tip 120. The helical grooves 32 are sized to accommodate the optical fibers along the length of the distal part 102 and accommodate the optical sensors at sensor locations spaced apart along the length L of the distal end portion 103. To simplify illustration, the three optical sensors 10 a, 10 b, 10 c are shown in FIG. 2 and FIG. 3 as spaced apart lengthwise on one side of the core wire. The sensors may preferably be distributed around the core wire, as shown, for example, in FIG. 4C and FIG. 4D. As illustrated, the multisensor guidewire 100 is capable of measuring blood pressure simultaneously at several points, in this case three points, using the three optic fiber-based pressure sensors 10 a, 10 b, 10 c arranged along the length L of the distal end portion 103 of the multisensor guidewire. For TAVI, the sensor locations are arranged to allow for the optical pressure sensors to be placed upstream and downstream of the aortic valve during measurements.

Accordingly, in this embodiment, the two more distal sensors 10 a and 10 b are spaced apart by a distance L₁ and sensors 10 b and 10 c are spaced apart by a distance L₂, where L₂>L₁. The dimensions and pitch/angle of the helical grooves 32 in the surface of the core wire 31 are selected to provide a space or channel between the grooved surface of the core wire 31 and coil 35. Each groove is deep enough that the fiber sits within the groove. Preferably, the grooves are sized so that the optical sensors 10 a and 10 b and the optical fibers 11 do not protrude beyond the external diameter D_(core) of the core wire 31. Each sensor and optical fiber may be fixed to the core wire, e.g. adhesively fixed to the core wire, at one or more points. For example, during assembly, optical fibers 11 are inserted into the grooves 32 and held in place in the grooves 32 in the core wire 31, e.g. with a suitable biocompatible and hemo-compatible adhesive, before the core wire is inserted into the coil wire 35. To accommodate the sensors 10 a, 10 b, 10 c and 20, which may be larger in diameter than the optical fibers 11 themselves, if required, each groove 32 may be enlarged to form a cavity or recess 34 in the region where the sensor is located, i.e. at each sensor location. As shown schematically in FIG. 2, the fine wire forming the flexible outer coil 35 of the distal portion 102 is tightly coiled along most of its length to form a tubular covering layer of the distal portion of the guidewire along most of its length. The guidewire coil 35 is more loosely coiled, or otherwise structured, in the distal end portion 103 to provide apertures 36 between the coils of the wire of the guidewire coil near each of the optical pressure sensors. The apertures allow for fluid contact with the optical pressure sensors 10 a, 10 b, and 10 c.

As shown in FIG. 3, a marker, such as a radiopaque marker 14, is provided near each sensor, e.g. placed in the helical groove 32 distally of the sensor, to assist in locating and positioning the sensors in use, i.e. using conventional radio-imaging techniques, when introducing the guidewire and positioning the sensors in a region of interest, e.g. upstream and downstream of the aortic valve. The radiopaque markers 14 are preferably of a material that has a greater radiopacity than the material of the core wire. For example, if the core wire 31 and outer coil 35 are stainless steel, a suitable heavy metal is used as a radiopaque marker, e.g. barium, tantalum, gold or platinum. However, if the core wire has sufficient radiopacity for visualizing and positioning the sensor arrangement in a region of interest, markers may not be required. If required, the coil of guidewire may have a conventional coating of a suitable biocompatible material, e.g. to facilitate insertion.

FIGS. 4A, 4B, 4C and 4D show enlarged axial cross-sectional views of the multisensor guidewire 100 taken through planes A-A, B-B, C-C and D-D respectively, of FIG. 2. FIG. 4A shows the four optical fibers 13 within the tubing 51 and jacket 52 of the proximal part 101. FIGS. 4B, 4C and 4D show the core wire 31 within the outer coil 35 to illustrate the location of the optical fibers 11 in grooves 32, and the location of pressure sensors 10 a, 10 c within enlarged groove portion 34 of the grooves 32 in the core wire 31.

Since the outer coil of the guidewire is quite flexible, the stiffness of the guidewire is determined predominantly by the stiffness of the core wire. Also, the optical fibers do not contribute significantly to the stiffness of the guidewire. For superior stiffness, which is required for a support guidewire of a given outside diameter, e.g. 0.89 mm, the outside diameter core wire is preferably as large as can be reasonably be accommodated within the inside diameter of the outer coil of the guidewire, allowing for the required clearance between the core wire and the outer flexible coil. Accordingly, the helical grooves 32 in the core wire preferably have a minimal size to accommodate the optical fibers and sensors within the grooves and within the diameter D_(core) of the core wire. In this context, by convention, the wire gauge or diameter D of a wire refers to the diameter D of the circle into which the wire will fit. It will be appreciated that the maximum diameter D_(core) must also fit within the inside diameter of the outer flexible coil of the guidewire, with an appropriate clearance between the core wire and optical fibers and sensors and the coil, which is, for example, at least 1 mil or 25 microns.

The helical form of the grooves 32 reduces longitudinal and point stresses/strains in the individual fibers when the guidewire is flexed. For example, if the grooves were straight along the length of the fiber, when the guidewire is flexed, optical fibers on the inside curve of the bend would be subject to more compressive forces and fibers on the outside of the curve would be subject to more tensile forces. While the ends of the fibers and the sensors may be adhesively fixed to the core wire within the grooves 32, and/or at one or more intermediate points, when the guidewire is flexed, the helical structure of the grooves tends to spread compressive and tensile forces over a length of each fiber and reduces localized stresses and strains. Thus it is preferably that the fibers have some freedom to move or slide within the grooves. Desirably, to optimize the core wire stiffness relative to the outside diameter of the guidewire, i.e. the diameter of the outer coil, there is a minimal required spacing between the core wire 31 and the coil 35, and therefore, preferably, the helical grooves are at least deep enough to accommodate the optical fibers and sensors without protruding beyond the diameter D_(core) of the core wire, as illustrated in the schematic cross-sectional view shown in FIG. 4B. As mentioned above, if needed, the grooves are enlarged to form a recess or cavity 34 in the sensor locations, as illustrated schematically in FIGS. 4C and 4D. The optical fibers and sensors are therefore protected within the grooves. The grooves are preferably formed with rounded or bevelled edges, i.e. to avoid sharp edges of the core wire that may damage the optical fibers and sensors during assembly or use. For similar reasons, the flexible outer coil may alternatively be formed from round wire rather than rectangular wire. To provide more protection to the optical fibers and sensors, the grooves may be deeper than the diameter of the fibers and/or sensors, provided the core wire can provide the required stiffness to the guidewire. Preferably, for a high stiffness guidewire, the core wire has a cross-sectional profile that defines grooves of the appropriate depth and dimensions to accommodate the optical fibers and optical sensors, while maximizing the cross-sectional area and effective diameter of the core wire.

The stiffness of a guidewire may be quantified by a flexural modulus, e.g. as described in an article by G. J. Harrison et al., entitled “Guidewire Stiffness: What's in a Name?” J. Endovasc. Ther. 2011, pp. 797-801. As an example, for, a stainless steel coil and core wire providing a guidewire having an outside diameter of 0.89 mm (0.035 inch), a TAVI guidewire desirably provides a flexural modulus of at least 60 GPa or 65 GPa. That would be similar to that of an Amplatz Super Stiff™ or Ultra Stiff™ guidewires (0.89 mm or 0.035 inch) which were reported in the above referenced article to have a flexural modulus of 60 GPa and 65 GPa, respectively. For some procedures, the operator may require or prefer a guidewire in the range 60 GPa±10%, or alternatively may require a significantly stiffer guidewire. For some procedures, e.g. a multisensor guidewire for diagnostic measurements only, a more flexible guidewire may be preferred.

FIG. 4A shows a corresponding cross-sectional view through the proximal portion 101, which comprises the bundle of optical fibers 13 contained within flexible tubing 51 and jacket 52. Since the proximal part 101 simply provides a flexible optical coupling to the control unit 150, it does not require the same stiffness or torque characteristics as the distal part 102 comprising the guidewire, and thus does not need to include a core wire. When the distal part is twisted or torqued to guide the guidewire intravascularly, a longer and more flexible proximal part 101 may assist with manoeuvrability of the guidewire.

The structure of the multisensor assembly is shown in cross-section along its length from the connector 112 to the distal tip 120 in FIG. 2. However for simplicity, the internal structure of the connector 112 is not shown. It will be appreciated that the optical fibers 13 of the proximal part 101 extend through the connector 112 to optical inputs/outputs 113 of the connector, as is conventional.

The optical pressure sensors 10 a, 10 b and 10 c are preferably Fabry-Pérot Micro-Opto-Mechanical-Systems (FP MOMS) pressure sensors. As an example, a suitable commercially available FP MOMS pressure sensor is the Fiso FOP-M260. These FP MOMS sensors meet specifications for an appropriate pressure range and sensitivity for blood pressure measurements. They have an outside diameter of 0.260 mm (260 μm). Typically, they would be coupled to an optical fiber with an outside diameter of 0.100 mm (100 μm) to 0.155 mm (155 μm). Accordingly, for 0.155 mm optical fibers, the helical grooves would have a depth of 0.155 mm along their length with an enlarged depth of 0.260 mm at each sensor location, plus any required clearances between the core wire and outer coil and around the fibers and the sensors. The pitch of the helical grooves is, for example, about 25 mm (1 inch) or more to reduce stress on the optical fibers.

As illustrated schematically in FIGS. 4B to 4D, assuming the coil 35 has an outside diameter of 0.89 mm (0.035 inch) including any coating, and is formed from 0.002 inch thick coil wire, which would provide a coil with an inside diameter of about 0.787 mm (0.031 inch), then a core wire having a maximum outside diameter of about 0.736 mm (0.029 inch) could be accommodated within, allowing for clearance between the core wire and the coil. Preferably the coil and the core of the guidewire are made from stainless steel having high stiffness and tensile strength, e.g. 304V stainless steel, or other approved types of stainless steel for medical applications. Other biocompatible metal alloys with suitable mechanical characteristics may alternatively be used. Typical medical grade nitinol alloys would not offer sufficient stiffness for a core wire for a multisensor support guidewire for transcatheter valve replacements. On the other hand, medical grade nitinol alloys may provide sufficient stiffness as a core wire for a multisensor guidewire for other percutaneous procedures where a more flexible guidewire is desirable, e.g. for intravascular insertion into smaller blood vessels or coronary arteries, or for a multisensor guidewire for diagnostic measurements only, such as described in the second embodiment. Since the fibers sit within the grooves of the core wire, for a guidewire of a given external diameter, e.g. 0.89 mm (0.035 inch), allowing for a standard thickness of the coil and the necessary clearance between the core wire and the coil, the core wire can have maximum outside diameter D_(core) similar to that of a core wire for a conventional support guidewire. The helical grooves are sized to accommodate standard optical fibers, e.g. standard low cost fibers of 0.155 mm diameter, or more preferably smaller diameter 0.100 mm optical fibers, as illustrated schematically in FIGS. 4C and 4D.

The helical grooves 32 will somewhat reduce the stiffness of the core wire relative to a conventional cylindrical core wire of the same outer diameter, but the grooved core wire structure accommodates multiple optical fibers and sensors while optimizing the stiffness for a given multisensor guidewire of a particular diameter. For example, as illustrated schematically in FIG. 4B, for 0.100 mm diameter optical fibers, the minimum diameter of the core wire D_(min), at the centre of the grooves, is approximately 0.5 mm, while the major part of the core wire (i.e. approx. 270°/360°=75%) has a maximum diameter D_(core) of 0.736 mm, which contributes significantly to the stiffness of the core wire.

By comparison, to accommodate a plurality of similarly sized optical fibers and sensors in a cylindrical space between a conventional core wire and the outer coil, the core wire diameter would have to be reduced to about 0.5 mm to accommodate the fibers, and even further reduced in the sensor locations to accommodate the sensors. Since the stiffness of a round core wire varies as the fourth power of the diameter, such a reduction in the core wire diameter significantly reduces the stiffness of the guidewire. While the helical grooves in the core wire 31 will somewhat reduce the stiffness of the core wire, they will do so by a far less significant factor than using a smaller diameter conventional core wire having a circular cross-section of 0.5 mm.

When helical grooves are provided to accommodate the fibers and the optical sensors, the pitch of the helix may be 25 mm (1 inch) or more, for example, to avoid excessive bending or stress/strain on the optical fibers. In alternative embodiments (not illustrated) the grooves in the guidewire run straight along the length of the guidewire, or run helically with a larger pitch. The feasibility of using helical grooves with a smaller pitch may be limited by optical fiber characteristics, such as acceptable optical fiber bend radius.

The multisensor support guidewire apparatus 100 is preferably also capable of measuring blood flow, since quantification of blood flow restriction is related to the pressure difference/gradient and the blood flow velocity. Thus, optionally, it includes an integral fiber-optic flow sensor 20 (see FIGS. 2 and 5B) at a suitable position in or near the distal end portion 103 to measure the blood flow velocity. The optical flow sensor comprises, for example, an optical thermoconvection sensor or other suitable optical flow sensor, coupled by a respective optical fiber to the optical/input output connector. The optional optical flow sensor 20 may comprise an optical thermoconvection flow sensor, e.g. as described in U.S. patent application Ser. No. 14/354,588.

The guidewire coil 35 together with the mandrel or core wire 31 provide the torquable characteristics of the multisensor support guidewire 100 so that is capable of being shaped or flexed to traverse vascular regions in a manner similar to that a conventional support guidewire. To facilitate insertion, the distal tip 120 extends beyond the distal end portion 103 containing the pressure sensors 10 a, 10 b, 10 c and optional flow sensor 20, and the tip 120 may be a flexible pre-formed J-tip or other appropriate atraumatic tip such as a resiliently deformable or flexible curved tip which is preformed or can be manually shaped. Typically the tip is contiguous with the guidewire. That is, the fine wire coil 35 extends along the length of the tip to a rounded end, and the core wire 31 is thinned within the tip to increase the flexibility of the tip relative to the main part of the support guidewire 102. The tip 120 may comprise a coating that can be pre-formed into a desired curved shape, e.g. a thermoplastic coating that can be thermoformed into a desire shape. Preferably, the core wire 31 has a maximum possible diameter within the coil 35 within distal end portion 103 that contains the sensors (e.g. see FIGS. 4B, 4C, and 4D) so that the distal part 102 of the guidewire has sufficient stiffness to act as a support guidewire for transcatheter valve replacements.

For operation of the optical sensors, the micro-coupler 140 couples the distal part 102 forming the multisensor guidewire to the proximal part 101 which provides optical coupling to the control unit 151 for controlling operation of the optical sensors 10 and 20. The proximal part 101 simply provides a flexible optical coupling of the distal part of the guidewire 102 to the control unit 151. Thus, the proximal part 101 can have any suitable diameter and flexibility. It is not required to have guidewire elements, i.e. a coil 35 and core wire 31 to provide specific mechanical properties of a guidewire, such as such as the stiffness and torque characteristics. Thus, the proximal part may be more similar to a lower cost optical fiber cable, e.g. a bundle of plurality of optical fibers 13 enclosed within a tubular covering layer 51, such as a single layer or multilayer flexible polymer tubing. If required, it is protected by a thicker protective outer jacket or sleeve 52 for mechanical strength/reinforcement and to facilitate handling. The optical fibers 13 in the proximal part are optically coupled to connector 112 at the proximal end 110 and to the micro-optical coupler 140 at the distal end.

The optical fibers 11 in the distal part 102 reduce the cross-sectional area of the core wire 31, therefore reducing stiffness of the guidewire 102. It will be appreciated that the use of specialized higher cost optical fibers 11 with a smaller diameter, e.g. 0.100 mm or less, and correspondingly sized smaller grooves, improves the stiffness of the core wire, and therefore the stiffness of the guidewire 102. On the other hand, to reduce overall cost, in the proximal part 101, standard lower cost optical fibers 13 with a larger diameter can be used, e.g. 0.155 mm diameter optical fibers used for telecommunication.

A multisensor guidewire 200 of a second embodiment is illustrated in FIGS. 5, 6 and 7A to 7E. Many elements of the multisensor guidewire 200 are similar to those of the multisensor support guidewire 100 illustrated in FIGS. 2 and 3 described above, and like parts are numbered with the same reference numeral. In this embodiment, the multisensor guidewire 200 comprises three optical sensors, that is, two optical pressure sensors 10 a and 10 b, an optical flow sensor 20, and their respective optical fibers 11. Accordingly, the core wire 131 has a cross-sectional profile comprising three grooves 32 along its length, to provide a guidewire having an axial cross-section as illustrated in FIGS. 7A, 7B, 7C and 7D. The grooves 32, and respective cavities 34 for the sensors, have a depth that accommodate the sensors 10 a, 10 b and 20, coupled to their respective optical fibers 11, within the diameter D_(core) of the core wire.

Referring back to FIG. 5, similar to the apparatus 100 shown in FIG. 2, the apparatus 200 comprises a proximal part 101 and distal part 102. The distal part 102 takes the form of a multisensor guidewire and comprises components of a conventional guidewire comprising a tubular outer layer in the form of a flexible fine metal coil 35 and an inner mandrel or core wire 131 within the outer coil 35. The outer diameter and mechanical properties of both the outer coil 35 and the core wire 131 are selected to provide the required stiffness to act as a guidewire for TAVI. Typically, for TAVI, the coil has an outside diameter of 0.035 inch or 0.89 mm or less, the guidewire has a suitable stiffness for transcatheter or intra-vascular insertion, and extends to distal tip 120, such as a flexible J-tip, or other atraumatic curved tip, to facilitate insertion.

As illustrated in the schematic cross-section shown in FIG. 7B, to accommodate three standard optical fibers of diameter 0.155 mm, the grooves take up a significant portion of the cross-sectional area of the core wire. By comparison, for a core wire of the same material and diameter D_(core), the structure shown in FIG. 4B will provide superior stiffness. As described for the apparatus 100 of the first embodiment, to provide the appropriate stiffness and mechanical properties for use as a support guidewire, coil 35 and core wire 131, are typically fabricated from a medical grade stainless steel, e.g. 304V. On the other hand, for other TVT procedures, e.g. if the multisensor guidewire is to be used only for diagnostic measurements, and not as a support guidewire for valve replacement, a high stiffness guidewire may not be required. For some TVT procedures, a more flexible guidewire may be preferred. In the latter case, other alloys may be suitable, e.g. medical grade metal alloys including nitinol, which are commonly used for cardiovascular guidewires.

As illustrated in FIG. 5 and FIG. 6, the coil wire 35 is closely wound along most of its length to form a tubular covering layer and in the distal end portion 103 containing the sensor arrangement 130, the coil wire is more loosely wound or structured to provide apertures 36 near each pressure sensor for fluid contact. The coil wire 35 in this embodiment is shown with a circular cross-section.

As shown in FIG. 5 and FIG. 6A, the distal part 102 contains a sensor arrangement 130 comprising the two optical pressure sensors 10 a and 10 b located within a length L of the distal end portion 103, near the distal tip 120. The optical flow sensor 20 is located proximally of the pressure sensors by a distance L_(FS). Internally, the distal part 102 provides optical coupling of the three optical sensors, through the plurality of optical fibers 11 to an optical coupling 145 at the proximal end of the guidewire.

For simplicity of illustration, the sensors 10 a, 10 b and 20 are shown in FIG. 6A as spaced apart lengthwise along one side of the core wire. In practice, since the grooves 32 are helical, the sensors may alternatively be distributed around the core wire 131 to position the sensors at the appropriate sensor locations and spacings.

FIG. 6B shows an enlarged and simplified schematic cross-sectional view through a central part of plane X-X of FIG. 6A, that is, along the axis of the helical groove 32. It will be appreciated that using the graphics software currently available to the Applicant, it was difficult to accurately illustrate the geometry of a cross-sectional slice of the core wire along helical groove X-X. FIG. 6B therefore shows a very simplified schematic, wherein the helical groove is represented as a straight so as to illustrate the positioning of the optical fiber 11 within the groove 32, with sensor 10 b within an enlarged part of the groove, i.e. cavity 34, so that both the fiber and the sensor can sit within the groove, protected within diameter D_(core). As illustrated schematically, the fiber 11 may be affixed to the core wire 131, e.g. in the groove 32 by adjacent the sensor 10 a, by a spot of adhesive or encapsulant 118.

The proximal part 101 of the apparatus 200 provides for optical coupling of the distal part 102 to the control unit 151 (e.g. see FIG. 1). Thus, the proximal part 101 contains a corresponding plurality of three optical fibers 13 which are optically coupled to optical fibers 11 of the distal part 102 at optical coupling 145. The proximal part has a tubular flexible covering layer 51 and a protective layer or jacket 52. The optical coupling 145 may be fixed or separable, and its body may be sized to form a handle or hub for manoeuvring the guidewire. The proximal part 101 has, at its proximal end 110, an optical input/output 112. In this embodiment, the optical input/output 112 takes the form of three optical connectors 114. Each optical fiber 13 of the proximal part is coupled through a flexible optical coupling, e.g. through a length of flexible tubing or optical cable 116, to an individual one of the three optical connectors 114. The latter may be conventional optical fiber connectors for ends 113 of each optical fiber.

As illustrated schematically in the enlarged longitudinal cross-sectional view in FIG. 6A, the three optical sensors 10 a, 10 b and 20, coupled to their respective optical fibers 11, are located in the distal end portion 103, near the distal tip 120. The sensors 10 a, 10 b and 20 are spaced by distances L and L_(FS) respectively. Each fiber 11 is secured to the core wire 131 at a point near each sensor, e.g. using a spot of adhesive 118 (see FIG. 6B). Preferably, the fibers 11 lie freely within their respective groove 32 along most of the length of the core wire, and they may be similarly secured to the core wire near the distal end. Thus, after assembly of the guidewire, each optical fiber has some freedom to move or slide within its groove when the guidewire is flexed or twisted, e.g. to spread stresses and strains along the length of each optical fiber.

During assembly, the fibers and sensors are affixed to the core wire to form a sub-assembly, which is then inserted into the flexible outer coil. For example, the fibers are secured to the surface of the core wire at a point adjacent each sensor, e.g. with a spot of adhesive within the groove, so that sensors are positioned at sensor locations with the required spacings, and/or so that each sensor is held within the sensor cavity of its groove. Since the grooves are helical, the optical fibers are wound around the core wire, so that the optical fibers are inserted into their respective groove around the core wire, and the proximal ends of the fibers are secured at the proximal end of the core wire. The sub-assembly of the core wire, sensors and their optical fibers is then inserted into the coil.

For protection of the sensors during assembly, it may be preferred to insert the sub-assembly from the distal end of the coil and subsequently form the optical connector at the proximal end, and then complete the distal tip. On the other hand, when the optical connector is pre-formed at the proximal end of the sub-assembly before insertion, the sensor end of the sub-assembly is inserted into the coil from proximal end of the coil. In either case, it is preferable that the guidewire components have rounded edges, i.e. to avoid sharp edges of the coil wire or core wire so that the subassembly with the sensors and optical fibers can slide smoothly into the outer coil without catching on sharp edges, to avoid mechanical damage to the sensors or optical fibers. For this reason, it is also preferable that the grooves are sufficiently deep that the fibers and sensors are protected within the grooves during assembly. For assembly, it may also be beneficial if the fibers are further secured, at least temporarily, in their grooves at multiple points along the length of the groove. However, in use of the multisensor guidewire, it is preferable that the fibers are fixed to the core wire adjacent the sensors but otherwise the fibers have some freedom to move or slide within the grooves when the guidewire is flexed.

If required, a marker, such as a radiopaque marker 14 is provided near each sensor, e.g. within the groove or cavity, to assist in locating and positioning the sensors in use, i.e. using conventional radio-imaging techniques, as described for the first embodiment. Apertures or openings in the coil wire adjacent the optical pressure sensors provide for fluid contact with the sensors. As mentioned for the first embodiment, if required, the outer coil of guidewire may have a coating of a suitable biocompatible coating, which may be, for example, a hydrophobic coating such as PTFE or silicone, or a hydrophilic coating. In some instances a hydrophilic distal tip may be preferred.

The spacings of the sensor locations are arranged for placement of a sensor each side, i.e. upstream and downstream, of a heart valve. As an example, for measuring a transaortic pressure gradient, the optical pressure sensors 10 a, 10 b, 10 c are arranged spaced apart by distances L₁ and L₂, e.g. 20 mm and 60 mm respectively, for placement of the sensors upstream and downstream of the aortic valve. The flow sensor 20 (see FIG. 5) is positioned proximally of the pressure sensors to measure flow in the aorta before the main branches from the aorta, e.g. in the ascending aorta, about 50 mm to 80 mm downstream of the aortic valve 511 or at a distance L_(FS) of about 20 mm to 30 mm from the nearest pressure sensor 10 b (see FIGS. 5 and 6A).

FIGS. 7A, 7B, 7C, 7D and 7E show enlarged axial cross-sectional views of the multisensor guidewire 200 taken through planes A-A, B-B, C-C, D-D and E-E respectively, of FIG. 5. FIG. 7A shows the optical fibers 13 with tubing 51 and jacket 52 of the proximal part 101. To accommodate optical sensors 10 a, 10 b and 20, and their respective optical fibers 11, while maintaining the required stiffness to the guidewire, the core wire has helical grooves 32 as shown in the axial cross-sectional views in FIGS. 7B, 7C and 7D. The grooves 32 extend along the length of the core wire 131 from the optical coupler 145 to near the distal tip 120.

The dimensions of the grooves 32 in the surface of the core wire 131 are selected to accommodate the fibers 11 in between the core wire 131 and coil 35. The grooves 32 are sized so that the optical pressure sensors 10 a, 10 b and 20 and the optical fibers 11 do not protrude beyond the external diameter D_(core) of the core wire 131 (see FIGS. 7B, 7C and 7D for example). Each sensor and optical fiber may be fixed to the core wire, e.g. adhesively fixed to the core wire, at one or more points. For example, during assembly, optical fibers 11 are adhesively attached to the core wire 131 near each sensor, e.g. with a suitable biocompatible and hemo-compatible adhesive 39, before the core wire is inserted into the coil wire 35. To accommodate the sensors 10 a, 10 b and 20, which may be larger in diameter than the optical fibers 11 themselves, if required, the grooves are enlarged in the region where the sensors 10 a, 10 b and 20 are located, i.e. to form a cavity or recess at each sensor location. For example, a cavity or recess 34 is ground in the core wire, as shown schematically in FIGS. 6, 7C and 7D, to provide space for the sensors 10 a, 10 b and 20. The guidewire coil 35 may be more loosely coiled, or otherwise structured, in the distal end portion 103 to provide apertures 36 between the coils of the wire of the guidewire coil near each of the optical pressure sensors that allow for fluid contact with the optical pressure sensors 10 a and 10 b.

FIGS. 7A, 7B, 7C, 7D, and 7E show schematic enlarged axial cross-sectional views of the multisensor guidewire 200 taken through planes A-A, B-B, C-C, D-D and E-E respectively, of FIG. 5 for a core wire sized to accommodate standard sized optical fibers, such as those used for telecommunications, having a diameter of 0.155 mm. Correspondingly, FIGS. 8A, 8B, 8C, 8D, and 8E show schematic enlarged axial cross-sectional views of the multisensor guidewire 200 taken through planes A-A, B-B, C-C, D-D and E-E respectively, of FIG. 5 for a multisensor guidewire with a core wire 231 sized to accommodate optical fibers having a smaller diameter, i.e. of 0.100 mm. Since the optical fibers do not contribute significantly to the stiffness of the guidewire, for superior stiffness required for a guidewire of a given outside diameter, e.g. ≦0.89 mm (0.035 inch), the diameter core wire D_(core) is preferably as large as can be reasonably be accommodated within the outer coil of the guidewire (e.g. D_(core)=0.029 inch) for a coil wire of 0.002 inch×0.012 inch. As illustrated schematically, if, for example, the optical fibers are of 0.100 mm (0.0039 inch) diameter, the grooves 32 in the core wire are sized accordingly to accommodate the optical fibers 11 in the space or channel between groove surface of the core wire 131 and outer coil 35. The three grooves are symmetrically spaced around the circumference of the core wire.

FIG. 9 shows a core wire 331 of an alternative embodiment, having another cross-sectional profile where the core wire surface is contoured, e.g. by wire drawing, to form two grooves 32 within the diameter D_(core) of the core wire, which can accommodate two optical fibers. As illustrated, and as mentioned above, in this context, for a wire with a cross-section that is not entirely circular, the diameter D_(core) of the core wire refers to the diameter of the circle into which the wire will fit. To avoid adversely affecting the torque characteristics of the core wire for guiding and steering the guidewire, the core wire preferably has rotational symmetry about the axis of the core wire. Thus, to accommodate a plurality of optical fibers, it is preferable that the groove structure of the core wire is has at least two fold rotational symmetry, as illustrated in FIG. 9 for core wire 331. More preferably, the core wire has three-fold or four-fold rotational symmetry. For example, core wire 431 shown in FIG. 10A has three grooves and accommodates three fibers, each within its own groove, and within the core wire diameter D_(core). Similarly, core wire 531 shown in FIG. 10B, has four grooves, each groove accommodating an individual optical fiber within the diameter D_(core). Thus, the core wire surface defines a cross-sectional profile that provides multiple grooves along the length of the core wire, each groove accommodating a single fiber and optical sensor, and with the grooves spaced symmetrically around the circumference of the core wire. Preferably, the grooves extend helically around the length of the core wire.

Advantageously, each optical fiber and its respective optical sensor are accommodated within an individual groove within the diameter D_(core) of the core wire to provide protection to the optical fibers and sensors during assembly and use. To facilitate fabrication, this enables the optical fibers carrying the optical sensors to be fixed to the core wire, e.g. by adhesively bonding the fibers to the surface of the core wire within a respective groove, to form an assembly of the core wire and the plurality of optical fibers and optical sensors, with the optical sensors appropriately spaced apart and positioned at the required sensor locations. Then, the assembly of the core wire, fibers and optical sensors can be inserted into the outer flexible coil. In preferred embodiments, the outer coil of the guidewire is fabricated from round coil wire, and all edges and surfaces of the grooves of the core wire and other components are radiused to avoid sharp edges that may catch on or damage the fibers and sensors during assembly.

Optical Micro-Coupler

The multisensor guidewire 100 of the first embodiment comprises a separable micro-optical coupler so that the distal part 102 comprising the multisensor support guidewire is separable from the proximal part 101 that provides an optical coupling to the control system. This arrangement enables proximal mounting of over-the-guidewire components, e.g. mounting of a replacement heart valve on the guidewire from the proximal end of the distal part 102 of the guidewire, in a manner similar to that used with a conventional support guidewire (i.e. without sensors).

That is, during known valve replacement procedures, such as TAVI, using a conventional support guidewire (i.e. without sensors), replacement valve components are mounted on the guidewire from the proximal end. For example, a support guidewire for TAVI is typically about 2.6 m to 3.0 m long and thus provides extra length at its proximal end to mount the valve components and delivery system on the guidewire. When the distal portion of the guidewire is initially introduced intravascularly into the patient, the extra proximal length of the guidewire holds the valve components and delivery system until the cardiologist is ready to introduce the replacement valve. However, since the optical multisensor guidewire must be optically coupled to the control system, if the distal part of the sensor guidewire is fixed to the larger diameter proximal part of the sensor guidewire, which carries the optical input/output connector for coupling to the control system, proximal mounting of components on the sensor guidewire is not possible.

For ease of manufacturing, ease of use, and user acceptance, it is advantageous if embodiments of the optical multisensor guidewire, as disclosed herein, can be manufactured and used in a manner that is similar to that for a conventional support guidewire. That is, it has an exterior form and characteristics, such as torque characteristics, similar to a conventionally structured support guidewire with which the medical staff is familiar, and which provides for proximal mounting of components over the wire in the usual manner. Accordingly, it is desirable to have a multisensor guidewire with separable distal and proximal parts that are coupled with a micro-optical coupler, such as described for the multisensor guidewire of first embodiment.

The micro-coupler 140 of the first embodiment will now be described in more detail with reference to FIG. 19. As illustrated in FIG. 19, the micro-coupler 140 comprises male and female parts, 142 and 144 respectively, to provide for optical coupling of each optical pressure sensor 10 a, 10 b, 10 c and optical flow sensor 20 via their respective individual optical fibers 11 of the distal part 102 to respective individual fibers 13 of the proximal part 101. Notably, the male portion 142 of the micro-optical coupler has the same outside diameter D as the coil 35 of the guidewire to enable components for transcatheter valve replacement to be mounted on or over the guidewire. The female portion 144 of the micro-optical coupler is of larger diameter and may be formed to act as a hub 44 that can be grasped facilitate handling and torque steering of the guidewire, and as well as to facilitate engaging and disengaging distal part 102. An alignment means, such as facet 43 of the male part 142, which aligns to a corresponding facet (not visible) in the female part 144 ensures that individual fibers 11 are indexed, aligned and correctly optically coupled to respective corresponding individual fibers 13 for optical data communication. The connector 140 may also include a suitable fastening means for securely attaching and locking/unlocking the two parts 142 and 144 of optical coupler 140.

FIG. 20 shows a cross-sectional view of the proximal end of distal part/guidewire 102 showing the internal structure of the male part 142 of connector 140. As illustrated schematically, the core wire 31 is tapered to form a core 37 at its end that inserts into the ferrule 42 of connector part 142 so that the individual optical fibers 11 are guided from the grooves 32 in the core wire 31 into and through the ferrule 42 of the connector part 142. The internal structure of the male connector part 142 is shown through lines A-A, B-B, C-C and D-D in subsequent FIGS. 21A, 21B, 21C and 21D.

Notably, the micro-coupler 140 provides for disengagement of the distal part 102 from the proximal part 101 of the guidewire. Moreover, the male part 142 has the same outside diameter D as the coil 35 of the multisensor guidewire. Thus, the distal part 102 functions as a conventional support guidewire, in that, components such as a replacement valve and delivery system, or other components, can be mounted on/over the guidewire from the proximal end for guiding and delivery into the heart.

The female part 144 of the micro-connector 140 may have an outer hub 44 of larger diameter to facilitate handling, alignment and connection of the micro-coupler 140.

The connector 140 enables the distal part 102 of the sensor guidewire to be unlocked from the proximal part 101, i.e. to untether the distal part 102 of the apparatus from the control console (control unit 151). Then TVT components can be inserted over the male part of the micro-coupler at the proximal end of the multisensor guidewire 102. Then the distal part 102 of the sensor guidewire is recoupled to the control console by proximal part 101, and the connector is locked so that the distal part 102 is again optically coupled to the control system for making pressure and flow measurements. The micro-coupler 140 therefore provides for proximal mounting, as is conventional, for components for transcatheter valve repair, such as, balloon catheters for valvuloplasty, and the multisensor guidewire additionally enables measurements of blood pressure, concurrently at multiple locations, and optionally also flow measurements, e.g. before and/or during and/or after a the valve repair procedure.

For multisensor support guidewires of embodiments comprising a separable optical micro-coupler, heart valve replacement or repair components, such as, a replacement heart valve and delivery device for TAVI, may be mounted over the multisensor guidewire from its proximal end. The multisensor guidewire has a standard length of a support guidewire, e.g. around 2.6 m.

Typically, a patient is evaluated some time (e.g. days or weeks) prior to valve replacement or repair (minimally invasive or open heart procedures), to determine whether valve repair or replacement is necessary or appropriate. Where diagnostic measurements of transvalvular blood pressure gradient and flow, and other parameters, have been performed previously, and confirm need for valve replacement, the valve components may be pre-mounted on the multisensor support guidewire ready to perform a transcatheter valve replacement procedure in a conventional manner. The multisensor guidewire can additionally provide data for blood pressure measurements at multiple locations, and/or flow measurements at any time before, during or after the procedure, or continuously during the procedure.

Optionally, it is envisaged that the multisensor guidewire would be introduced initially for diagnostic measurements of a transvalvular pressure gradient and blood flow. If, for example, measurements confirm the need for an immediate valve replacement or repair, the micro-coupler is separated to enable proximal mounting of components over the guidewire, e.g. for further assessment, or for delivery of a replacement heart valve or repair components. The micro-coupler is then reconnected to enable similar diagnostic measurements of the transvalvular pressure gradient and blood flow to be made before or after the procedure, or continuously prior to the procedure, during the procedure, and for a monitoring period afterwards.

Alternative Embodiments

For multisensor guidewires of some embodiments, for example, as illustrated in FIG. 5, for the multisensor guidewire 200 of the second embodiment, the optical micro-coupler connecting the proximal part 101 and distal part 102 may be replaced with a larger optical coupling 145, either a separable optical coupler or fixed coupling. The body of optical coupling 145 may be sized to act as a handle or hub for insertion and torque steering of the guidewire. In the latter arrangement, any components for insertion, such as a replacement heart valve, would be placed over the guidewire from the distal tip, before intravascular insertion of the guidewire into the patient.

Conventionally, a typical length of standard guidewire is around 1.8 m. A support guidewire for transcatheter valve replacement is not only stiffer to hold the components firmly during delivery of the replacement valve, it has additional length, e.g. a total length of approximately 2.8 m. Thus, when the distal part of the guidewire is initially inserted into the patient, the additional length at the proximal end holds the heart valve components until the cardiologist is ready to deliver and insert the valve.

For the multisensor support guidewire 100 illustrated in FIG. 2, a single optical connector 114 is shown for the input/output 112 for each of the optical fibers 13. In other embodiments, an alternative connector or coupling arrangement may be provided. The optical input/output 112 and the control unit port 153 may comprise several individual optic fiber connectors, e.g. as illustrated in FIG. 5 for the multisensor guidewire 200 of the second embodiment. In further embodiments, not illustrated, the input/output 112 may optionally include circuitry allowing wireless communication of control and data signals between the multisensor guidewire and the control unit 151. Optionally one or more electrical connectors for peripheral devices, or for additional or alternative electrical sensors, may be provided.

Referring to FIG. 11A, this shows schematically the placement of the distal end portion 103 of the guidewire 102 within the left ventricle 512 in the human heart 500. For transcatheter valve replacement procedures, the distal tip 120 is preferably of a suitable structure, such as a flexible and specially curved tip or J-tip, to assist in firmly anchoring the distal end of the guidewire in position in the ventricle, without causing trauma to the ventricular wall, the valve or other tissues within the heart. Anchoring of the guidewire, in a stable but atraumatic manner, is particularly important during valve replacement procedures, i.e. to ensure accurate and optimum placement of replacement valve and to hold the valve in position during valve implantation and/or during other therapeutic or diagnostic procedures before or after implantation. This also facilitates precise positioning of the sensors in the region of interest for more accurate and reliable measurements of parameters such as blood pressure, transvalvular pressure gradient, and blood flow, before, during and/or after the transcatheter valve replacement procedure.

FIG. 11B shows a schematic diagram of a human heart 500 to illustrate placement within the left ventricle 512 of a multisensor guidewire 102, similar to that shown in FIG. 5, for use as both: a) a guidewire during a TAVI procedure and b) for directly measuring a blood pressure gradient across the aortic heart valve 511 before and after the TAVI procedure, wherein a flow sensor 20 is provided for measuring blood flow upstream of the aortic valve 511. The multisensor guidewire 102 comprises two optical pressure sensors 10 a, 10 b, which are spaced apart by a suitable distance, e.g. at least 20 mm to 50 mm apart and more preferably about 70 mm to 80 mm apart, so that one sensor can be located upstream and one sensor located downstream of the aortic valve 511. The flow sensor 20 is located further downstream of the aortic valve 511, in the root of the aorta, e.g. a distance L_(FS) of about 20 mm to 30 mm from the nearest pressure sensor 10 b.

For example, a sensor spacing of about 20 mm to 50 mm would be sufficient to place one sensor upstream and one downstream of a heart valve. However, blood pressure measurements may be affected by significant turbulence in the blood flow through the cardiac cycle. For this reason, a larger spacing, e.g. 70 mm to 80 mm, between the two sensor locations may be preferred to enable one sensor to be located further into the ventricle and another sensor to be located further upstream of the valve in the aorta, so that both sensors are located in regions of less turbulent flow, i.e. spaced some distance each side of the valve. Based on review of CT scans to assess dimensions of the heart of a number of subjects, an 80 mm spacing of two pressure sensors may be preferred. For paediatric use, a closer spacing of the sensors may be preferred.

For comparison, FIGS. 12A, 12B and 12C show, schematically, three approaches for positioning of the distal end portion 103 of the guidewire 102 through the mitral valve 513. Correspondingly, FIGS. 13 and 14 show placement through the tricuspid valve 522 and through the pulmonary valve 224, respectively. Each of these Figures indicates how the three optical pressure sensors 10 a, 10 b, 10 c would be placed for measurement of a transvalvular pressure gradient.

In practice, it is desirable that a multisensor guidewire provides a plurality of optical pressure sensors, e.g. two or three pressure sensors, and optionally a flow sensor, that are optimally spaced for measurement of transvalvular pressure gradients and flow for any one of the four heart valves. For example, while multisensor guidewires may be individually customized for different TVT procedures, or, for example, smaller sized versions may be provided for paediatric use, it is preferred to have a standard arrangement, e.g., two, three or four sensors, which is suitable for various diagnostic measurements and for use during various TVT procedures.

Transvalvular Pressure Measurements in Interventional Cardiology

By way of example only, the use of a multisensor guidewire for transvalvular pressure measurement will be described with reference to the multisensor guidewire 100 of the first embodiment, and with reference to the aortic valve. For measuring and monitoring the blood pressure gradient across the aortic valve 511, i.e. the aortic transvalvular pressure gradient in a human heart 500 (see FIG. 11A), a conventional guidewire is first inserted into a peripheral artery, such as the femoral, brachial, or radial artery, using known techniques, and advanced through the ascending aorta 510 into the left ventricle 512. A catheter is then slid over the guidewire. The operator then advances and positions the catheter into the left ventricle 512, using a known visualization modality, e.g. X-ray imaging along with radio-opaque markers 14 on the distal end, or contrast agent. The operator then replaces the guidewire with the multisensor guidewire 100 in the lumen of the catheter. The operator advances the multisensor guidewire 100 through the catheter and positions the distal end portion 103 of the multisensor guidewire 100 into the left ventricle 512 using visualization devices such as the radio-opaque markers 14 on its distal end 103. Then, the operator pulls back the catheter over the guidewire. Once the multisensor guidewire 100 is properly positioned, and is coupled to the control unit 151 to activate the optical sensors, the optical pressure sensors 10 a, 10 b and 10 c directly measure the transvalvular pressure gradient of the aortic valve 511. As illustrated schematically in FIG. 11A, two pressure sensors 10 a, 10 b are positioned in the left ventricle 512 and one pressure sensor 10 c is positioned in the aorta 510 just downstream of the aortic valve 511, to allow simultaneous measurements of pressure at three locations, i.e. both upstream and downstream of the valve. A series of measurements may be taken during several cardiac cycles. Although not illustrated in FIG. 11A, a flow sensor 20 may also be provided for simultaneous flow measurements. Measurements results may be displayed graphically, e.g. as a chart on the touch screen display 152 of the system controller 150 (see FIG. 1) showing the pressure gradient and flow. The control system may provide for multiple measurements to be averaged over several cycles, and/or may provide for cycle-to-cycle variations to be visualized. Thus, the operator can quickly and easily obtain transvalvular pressure gradient measurements. The valve area may also be computed when blood flow measurements are also available. Measurements may be made, for example, before and after valve replacement or valve repair procedures.

FIGS. 16A, 16B and 16C and FIGS. 17A, 17B and 17C are simplified schematics of the aortic heart valve 511 and left ventricle 512, illustrating the concept of aortic transvalvular pressure gradient as measured by the multisensor guidewire 100 using the method of the first embodiment described above, for a healthy heart and for a heart with stenoses 531, 532 and 533. In this particular example, the aortic transvalvular pressure gradient is the blood pressure measured by sensors at locations P1, P2 within the left ventricle 512 and P3 within the aortic root 510.

The function of the heart is to move de-oxygenated blood from the veins to the lungs and oxygenated blood from the lungs to the body via the arteries. The right side of the heart collects de-oxygenated blood in the right atrium 521 from large peripheral veins, such as, the inferior vena cavae 520. From the right atrium 521 the blood moves through the tricuspid valve 522 into the right ventricle 523. The right ventricle 523 pumps the de-oxygenated blood into the lungs via the pulmonary artery 525. Meanwhile, the left side of the heart collects oxygenated blood from the lungs into the left atrium 514. From the left atrium 514 the blood moves through the mitral valve 513 into the left ventricle 512. The left ventricle 512 then pumps the oxygenated blood out to the body through the aorta 510.

Throughout the cardiac cycle, blood pressure increases and decreases into the aortic root 510 and left ventricle 512, for example, as illustrated by the pressure curves 630 and 640, respectively, in FIG. 15, which shows curves typical of a healthy heart. The cardiac cycle is coordinated by a series of electrical impulses 610 that are produced by specialized heart cells. The ventricular systole 601 is the period of time when the heart muscles (myocardium) of the right 523 and left ventricles 512 almost simultaneously contract to send the blood through the circulatory system, abruptly decreasing the volume of blood within the ventricles 620. The ventricular diastole 602 is the period of time when the ventricles 620 relax after contraction in preparation for refilling with circulating blood. During ventricular diastole 602, the pressure in the left ventricle 640 drops to a minimum value and the volume of blood within the ventricle increases 620.

The left heart without lesions, illustrated in FIGS. 16A, 16B and 16C, would generate aortic and ventricular pressure curves similar to curves 630 and 640, respectively, in FIG. 15. However, the heart illustrated in FIGS. 17A, 17B and 17C has multiple sites of potential blood flow 530 obstructions 531, 532 and 533. In some cases, the operator of the multisensor guidewire 100 might want to measure the blood pressure at several locations, within the root of the aorta 510 in order to assess a subvalvular aortic stenosis 533 or a supravalvular aortic stenosis 531.

The cardiac hemodynamic data collected from a patient's heart allow a clinician to assess the physiological significance of stenosic lesions. The aortic and ventricular pressure curves from a patient's heart are compared with expected pressure curves. FIG. 18 illustrates typical differences between the aortic 630 and ventricular 640 pressure curves due to intracardiac obstructions. Some of those variations include the maximal difference 605 and the peak-to-peak difference 606 between curves 630 and 640. The area 607 between the aortic pressure curve 630 and ventricle pressure curve 640 is also used to assess the physiological significance of stenosic lesions. The difference between the amplitude 603, 604 of the aortic 630 and ventricle 640 pressure curves is also key information for the clinician.

The medical reference literature relating to cardiac catheterization and hemodynamics provides different possible variations of the aortic 630 and ventricular 640 pressure curves along with the possible causes in order to identify the proper medical diagnosis. For example, cardiac hemodynamic curves, such as shown in FIG. 18, along with analysis of the curves, are provided on pages 647 to 653 of the reference book entitled Grossman's cardiac catheterization, angiography, and intervention by Donald S. Baim and William Grossman.

As indicated, when the valve is closed as shown in FIG. 16A, the pressures P1 and P2 measured by first and second sensors 10 a and 10 b placed in the left ventricle would be equal and lower than the pressure P3 measured by the third sensor in the aorta during the ventricular diastole 302. During the ventricular systole 301, when the aortic valve begins to open, FIG. 16B, the pressures P1, P2 and P3 increase and when the aortic valve is fully open, FIG. 16C, P1, P2 and P3 are similar. The specific form of the pressure traces P1, P2, P3 generated by each sensor provides the interventional cardiologist with direct, real-time data to aid in diagnosis and assessment of valve performance before and after TVR.

However, as illustrated schematically in FIGS. 17A, 17B and 17C, when the heart has subvalvular aortic stenosis 533, for example, the pressure traces P1, P2 and P3 will differ. To detect and assess the severity of subvalvular stenosis 533, the two distal pressure sensors at locations P1 and P2 must be located in the left ventricle on each side of stenosis 533 while the proximal pressure sensor P3 must be located within the root of the aorta 510 at a certain distance from the aortic valve 511. Therefore, as shown, the distance L₁ (typically about 20 mm) between sensors 10 a, 10 b is shorter than the distance L₂ (typically about 50 mm or 60 mm) between sensors 10 b, 10 c, which length is determined by the dimensions of the heart or vascular region to be monitored. As illustrated schematically in FIGS. 17A, 17B and 17C, when the heart has subvalvular aortic stenosis 533, for example, the pressure traces P1, P2 and P3 will differ.

Importantly, the specific positioning of the multiple sensors enables measurements that permit the determination of whether the stenosis is strictly associated with the valve or not, and whether it is associated with a subvalvular stenosis (e.g. sub-aortic hypertrophic stenosis) or supravalvular stenosis. It also enables measurements that permit the determination of the functional severity of subvalvular stenosis.

Manufacturability

During prototyping, a number of challenges have been discovered in attempting to accommodate a plurality of optical sensors and optical fibers within a multisensor support guidewire having a required stiffness e.g. 60 GPa, and a sufficiently small outside diameter ≦1 mm, and typically 0.89 mm or 0.035 inch, for use in TVR, including TAVI. Until smaller diameter optical sensors and optical fibers are developed and characterized, a design of core wire is required to accommodate multiple fibers and sensors without unduly reducing the stiffness of the core wire.

In considering manufacturing tolerances for the optical components and for the guidewire coil and core wire, it has also been discovered that there are currently significant manufacturing challenges in providing multisensor guidewires of diameter ≦1 mm comprising a grooved core wire which accommodates multiple optical fibers and optical sensors.

Conventionally, core wires are circular in cross-section and manufactured by standard wire-drawing and/or wire-rolling processes, e.g., from suitable metals and alloys, usually medical grade stainless steel, or nitinol, to provide the required mechanical properties, e.g., stiffness, flexibility, tensile strength. Thus, conventionally, small diameter round core wires with sufficient stiffness for support guidewires are manufactured by drawing (pulling) a wire through successively smaller dies.

Manufacturing a sub-millimeter diameter core wire with straight or helical grooves along its length to accommodate individual optical fibers of approximately 100 μm diameter, presents challenges for conventional core wire manufacturing facilities.

Since medical guidewires are intended to be disposable, i.e. for single-use only, an alternative or lower cost manufacturing solution is desirable. However, for medical applications, it will also be appreciated that manufacturing facilities must also be capable of meeting required regulatory standards for medical devices. It also desirable to use materials, e.g., metals and alloys, such as medical grade stainless steel, which already have regulatory approval for medical use and for which extensive manufacturing experience is already available. It is envisaged that alternative materials, such as suitable polymer and composite materials could potentially be used for manufacture of core wires, e.g. if they provide appropriate stiffness and mechanical properties. However, conventional medical grade metals and alloys, that already have regulatory approval for medical use, are preferred.

During initial prototyping, the Applicant encountered several manufacturing challenges that had to be overcome in order to manufacture grooved stainless steel core wires of the required size and tolerances by known wire drawing processes, particularly with respect to forming a plurality of small grooves to accommodate individual fibers, and controlling rotation of grooves along the length of the wire, e.g. to form helical grooves of a pre-defined pitch.

For manufacturing reasons, a core wire having a single channel or groove accommodating multiple fibers was proposed the above referenced U.S. Provisional patent application No. 62/039,952, entitled “System And Apparatus Comprising a Multisensor Support Guidewire for Use in Trans-Catheter Heart Valve Therapies”, filed Aug. 21, 2014. For example, a core wire was disclosed having a D-shape cross-section or a contoured/scalloped groove for three fibers. However, a core wire with single groove containing multiple fibers along one side of the core wire is not optimum for providing rotationally symmetric torque characteristics. It was also discovered that, this structure did not effectively protect the optical fibers and sensors from damage during assembly since the optical components are exposed and tend to be dislodged, or catch on inner surfaces of the coil, during insertion of the core wire/optical fiber assembly into the coil, leading to damage of the optical components.

Accordingly, as disclosed herein, for an optical multisensor guidewire, beneficially the core wire has a plurality of grooves, spaced with rotational symmetry around the core wire, wherein each groove accommodates an individual optical fiber and its optical sensor. The grooves preferably have some rotation around the core wire, i.e. are helical, and are deep enough to accommodate the optical fibers within the diameter of the core wire, for protection of the optical fibers and sensors from mechanical damage during assembly and in use.

To facilitate manufacturing, it is desirable that the grooved core wire has a cross-sectional profile that can be formed by a wire-drawing process, i.e. similar to the processes currently used in manufacturing conventional round core wires for medical guidewires. The wire-drawing process may use high precision diamond wire drawing dies, as manufactured by Fort Wayne Wire Die, Inc. For example, surfaces of the core wire defining the grooves are radiused with at least a minimum radius for formation of the core wire by wire-drawing.

In embodiments described above, the outer flexible tubular member 35 of the guide wire, which is referred to as the outer flexible coil, or “coil”, is disclosed as a being wound from a coil of fine metal wire, i.e. a round or rectangular wire as illustrated in FIG. 2 and FIG. 5. It is also known, to form at least part of outer flexible tubular member from a flexible metal hypotube. That is, a metal hypotube that is spirally cut or slotted to provide the required flexibility, as described for example, in U.S. Pat. No. 6,107,004, The hypotube is, for example, stainless steel or nitinol, which is cut using processes, such as, laser cutting, laser microject cutting, electrostatic discharge machining (EDM), and chemical milling or etching. The term “coil”, as used herein, is therefore intended to encompass an elongate flexible tubular member comprising a conventional outer coil of a guidewire wound from fine wire and/or a spirally cut metal hypotube and/or a slotted metal hypotube, and combinations thereof.

It is envisaged that in the future, a technique such as laser cutting may potentially be used for formation of the grooved core-wire.

During assembly, the optical fibers and sensors are assembled and secured to the core wire, e.g. adhesively bonded, at least at one point near each sensor. Then, the sensor assembly, comprising the optical fibers and sensors secured to the core wire, is inserted into the outer coil. It is desirable to protect the optical fibers and sensors during assembly, and for this reason, it is preferred to provide an individual groove for each optical fiber and sensor, and for the groove structure to be sufficiently deep to entirely accommodate the fiber and the sensor within the diameter D_(core) of the core wire. As mentioned above, it is also desirable to avoid sharp edges, and provide all components, including the coil wire and the core wire, with rounded edges to facilitate assembly, i.e. that the sub-assembly can slide smoothly into the coil, without catching on sharp edges, and also to protect the sensors and optical fibers from damage when the guidewire is flexed during use. Also, as explained above, it is preferable that the cross-sectional shape of core wire has at least three-fold rotational symmetry, and that the grooves have some rotation around the core wire, preferably extending helically around the core wire, for improved torque characteristics of the guidewire, and to distribute stresses/strains on the fibers when the guidewire is flexed.

Other factors for consideration are: regulatory requirements for medical devices, ease of use and safety. For these reasons, it is desirable that the multisensor guide wire is based on a conventional tried and tested external guidewire structure, i.e. based on a predicate device structure comprising an external flexible coil and core wire, which has regulatory approval and which is fabricated with materials, such as 304V stainless steel or nitinol, that already have regulatory approval for medical use in guidewires. It is also desirable that the multisensor guidewire can incorporate known safety features of conventional guidewires. For example, they are fabricated from materials having high tensile tensile strength to minimize the likelihood of stretching or fracturing, and typically include a structure such as a safety ribbon, which extends along its length and is welded to both ends of the guidewire to reduce the risk of separation of fragments in case of fracture.

As mentioned above, the grooved core wire structure also protects the optical fibers and sensors from mechanical damage during assembly and use. When each optical sensor sits fully within its groove in the core wire, or within an enlarged portion of the groove at the sensor location, the grooved core wire structure helps to reduce the risk of breakage or separation of the optical components in use. Also, each fiber is preferably adhesively bonded or otherwise secured to the core wire in the groove adjacent the respective optical sensor. This ensures the sensors are appropriated positioned and fixed in the sensor locations, i.e. at the required sensor spacing as well as retained within the groove to protect them from damage. When the sensors are bonded to the ends of the fibers, rather than integrally formed at the end of the fiber, if required, some additional adhesive or encapsulation material may be provided in the groove to protect and strengthen the junction/bond region between the fiber and sensor, e.g. to reduce risk of separation of the sensor from the fiber. For similar reasons, apertures in the coil wire adjacent the optical pressure sensor should be large enough to enable fluid contact for accurate sensing of blood pressure, but preferably, the apertures are sized to ensure that if an optical sensor were to separate, it would be captured and retained within the coil wire.

As mentioned above, a helical groove structure also helps to spread stresses and strains on the optical fibers along their length when the guidewire is flexed in use. For this reason, it may be preferred to fix the optical fibers only at ends of the guidewire, e.g. a spot of adhesive or encapsulant near sensor locations and another spot at the proximal end near the input/output connector. Each fiber then has some freedom to move or slide within its groove as the guidewire is flexed. This arrangement provides for the optical sensors to be secured in their respective sensor locations, at predetermined sensor spacings, so that pressure gradients can be accurately obtained.

Contact Force Sensor

Beneficially, for use in TVR, the multisensor guidewire 100 is also capable of measuring a contact force of the guidewire against the wall of the heart, e.g. the wall of a diseased left ventricle. Thus, a guidewire according to another embodiment comprises an integral fiber-optic contact force sensor 60 as illustrated schematically in FIGS. 22, 23, 24, 25A and 25B, e.g. an optical strain gauge type of sensor, located at a suitable position in or near the distal end portion 103. For example, as illustrated in FIGS. 22 and 23, the optical contact force sensor 60 comprises a Fabry-Pérot MOMS sensor 61 which is located in the distal end portion 103 and is coupled by a respective optical fiber 11 to an input output optical connector, e.g. to the micro-optical connector 140 as previously described. The cavity 62 and diaphragm 63 of the Fabry-Pérot MOMS sensor 61 is also coupled to a length L_(CS) of a second optical fiber 64 which extends from the sensor 61 along the length L_(CS) of the distal end of the guidewire, towards the flexible tip 120. As illustrated in FIGS. 25A and 25B, the second optical fiber 64 sits in a helical groove 32 in the core wire which is enlarged to form a recess 34 at A-A to accommodate the sensor 61. As indicated in FIG. 23, the sensor 61 and the end of fiber 64 are fixed to the core wire at points 66. This arrangement allows for the sensor 61 to detect and measure a contact force applied along a length L_(CS) of the guidewire when it contacts the internal heart walls 215 of the heart as indicated schematically in FIG. 24. Such a contact force sensor 60 provides information and feedback to the cardiologist regarding the force F being applied, e.g. when a detected contact force approaches or exceeds a threshold F_(t) that may cause tissue damage, or potentially even cause fatal injuries during TVR, an alert may be provided to the operator.

Thus, for example, the guidewire 100 may comprises three optical pressure sensors 10 a, 10 b, 10 c as described above with reference to FIGS. 2 and 3, optionally a flow sensor 20 located in the distal end portion, and a contact force sensor 60 located in a region between the distal end portion 103 containing the optical pressure sensors and the flexible distal tip 120, to sense a contact force applied near the end of the guidewire, along the length L_(CS) indicated by the dotted line in FIG. 26.

Flexible Preformed Three-Dimensional Curved Tip

To assist in atraumatic insertion and anchoring of the guidewire 100 within the ventricle during TVR, it is desirable to use a flexible preformed tip such as a J-tip or other curved tip. FIGS. 27A and 27B show two views of a pre-formed flexible tip 400-1 having a three-dimensional form, specifically in this embodiment, a pre-formed helical tip, of coil diameter D_(T), e.g. 5 cm, which resembles part of a telephone cord or a pigtail. A tip 400-2 of another embodiment, as illustrated in FIGS. 29A and 29B, comprises a pre-formed helix that is tapered to resemble the form of a snail shell. FIGS. 28 and 30, respectively, represent schematically the placement of these pre-formed helical tips 400-1 and 400-2 in the left ventricle 512 for TVR or for diagnostic measurements using the optical pressure sensors 100. This three-dimensional pre-formed structure is proposed for improved support of the guidewire in each of the X, Y and Z directions during TVR procedures. Such a structure can assist in providing support for the guidewire in a safer manner.

Further Embodiments

It will be appreciated that in alternative embodiments or variants of the multisensor guidewires of the embodiments described in detail above, one or more features disclosed herein may be combined in different combinations or with one or more other features disclosed herein and in the related patent applications referenced herein, depending on whether the multisensor guidewire is to be used as a multisensor support guidewire for transcatheter valve replacement, requiring a guidewire with high stiffness, or, as a multisensor guidewire for other TVT procedures where a more flexible multisensor guidewire is preferred.

In preferred embodiments, the multisensor guidewire comprises a core wire having multiple helical grooves along its length to accommodate a plurality of three or four optical sensors and optical fibers within a required maximum core wire diameter D_(core). For support guidewires for TVR, the guidewire can then be provided with the required stiffness, e.g. a flexural modulus of ˜60 GPa, in a guidewire having a diameter of ≦0.89 mm external diameter. Preferably the grooves are symmetrically arranged around the core wire and extend helically along the length of the core wire for rotationally symmetric stiffness and torque characteristics.

Additionally, for valve replacement, since the guidewire must be firmly anchored within the ventricle for accurate measurements and for positioning of a replacement valve, an optional three-dimensional pre-formed curved tip, such as a pre-formed “snail” tip, assists in positioning and anchoring the distal end of the multisensor guidewire in the ventricle during TAVI.

Furthermore, an optional contact force sensor near the tip provides important feedback to the interventional cardiologist relating to the force being applied or transferred internally to tissues of the heart wall. Feedback to the cardiologist to indicate when a contact force exceeds a threshold level, together with a specially shaped pre-formed flexible tip, assists in reducing trauma to the tissues of the heart, and in particular reduces risk of perforation the ventricular wall.

In a multisensor guidewire for percutaneous, minimally invasive intravascular procedures other than transcatheter valve replacement, which do not need the high stiffness of a conventional support guidewire, a more flexible multisensor guidewire may be desirable. For example, for initial diagnostic measurements within the heart, including transvalvular blood pressure measurements, a smaller diameter and/or more flexible and/or shorter multisensor guidewire may be appropriate. As an example, the latter may also be applicable for percutaneous, minimally invasive intravascular procedures such as diagnostic measurements requiring concurrent pressure measurements at multiple locations within smaller blood vessels, or within the coronary arteries for assessment of stenotic lesions.

Thus, the interventional cardiologist is offered multisensor guidewires according to various embodiments, which can be configured for intravascular diagnostic measurements and/or as a support guidewire for transcatheter valve replacement procedures, including TAVI. Options including a contact force sensor and a three dimensional atraumatic tip help to avoid trauma or perforations.

INDUSTRIAL APPLICABILITY

Currently, patient mortality rate after TAVI is significant, with some studies reporting mortality in a range of 10%-15%. As shown by a growing number of studies, interventional cardiologists need accurate data, i.e. measurements of cardiovascular parameters to assess the functional performance of a patient's heart valves before and after TAVI, to obtain a better understanding of the issues and to find solutions to reduce mortality and reduce the need for re-intervention after TAVI.

Systems and apparatus according to embodiments of the invention comprise multisensor support guidewires for use in transcatheter valve replacements, such as TAVI. These Smart Guidewires™ not only have the required mechanical characteristics to act as support guidewires for transcatheter valve replacements, they comprise sensors for making direct (in-situ) measurements of important parameters, including measurement of blood pressure concurrently at multiple locations within the heart, to obtain a transvalvular blood pressure gradient and optionally also measure blood flow, for evaluation of performance of the heart and the heart valves immediately before and after transcatheter valve replacement. A single-use disposable guidewire integrating multiple optical sensors allows for quickly providing real-time accurate quantitative data related to functional performance of heart valves right before and after TVT.

Although embodiments of the invention have been described and illustrated in detail, it is to be clearly understood that the same is by way of illustration and example only and not to be taken by way of limitation, the scope of the present invention being limited only by the appended claims. 

1. A multisensor guidewire for measuring blood pressure concurrently at multiple locations during a minimally invasive intravascular or cardiac intervention, comprising: a tubular covering layer comprising a flexible coil (coil), the coil having a length extending between a proximal end and a distal end, an outside diameter of ≦1 mm, a core wire extending within the coil from the proximal end to the distal end, and the distal end comprising a flexible distal tip; a plurality of optical sensors and a plurality of optical fibers; a sensor end of each optical fiber being attached and optically coupled to an individual one of the plurality of optical sensors; the core wire having an external surface with a cross-sectional profile defining a plurality of grooves extending along a length of the core wire, each groove accommodating an individual optical fiber and a respective optical sensor within a diameter D_(core) of the core wire and providing a sensor arrangement with said plurality of optical sensors positioned at respective sensor locations within a distal end portion of the guidewire; a proximal end of each of the plurality of optical fibers being coupled to an optical input/output connector at the proximal end of the guidewire for connection to an optical control system; and the plurality of optical sensors of the sensor arrangement including at least two optical pressure sensors at respective sensor locations spaced apart lengthwise along a length of said distal end portion.
 2. The multisensor guidewire of claim 1, wherein the plurality of grooves are symmetrically spaced around the core wire.
 3. The multisensor guidewire of claim 2, wherein the grooves are helical grooves.
 4. The multisensor guidewire of claim 3, wherein the helical grooves have a pitch of at least 25 mm (1 inch).
 5. The multisensor guidewire claim 1, wherein the grooves have a depth that accommodates each optical fiber and optical sensor within a respective groove of the core wire without protruding beyond the diameter D_(core) of the core wire.
 6. The multisensor guidewire of claim 5, wherein, at sensor positions in the distal end portion, the grooves are enlarged to accommodate optical sensors having an external diameter greater than that of the optical fibers.
 7. The multisensor guidewire of claim 1, wherein surfaces of the core wire defining the grooves are radiused to no less than a minimum radius R_(min) for formation of the grooves by a wire-drawing process.
 8. The multisensor guidewire of claim 1, wherein each optical fiber is adhesively bonded to the core wire within its respective groove at a point adjacent the sensor location.
 9. The multisensor guidewire of claim 1, wherein the coil has an outside diameter of ≦0.89 mm (≦0.035 inch).
 10. The multisensor guidewire of claim 1, for use as a support guidewire for transcatheter valve replacement, wherein the core wire comprises a medical grade stainless steel alloy and the diameter D_(core) of the core wire provides the guidewire with predetermined stiffness characteristics defined by a standard guidewire descriptor, said guidewire descriptor being one of stiff, super-stiff and ultra-stiff.
 11. The multisensor guidewire of claim 1, for use as a support guidewire for transcatheter valve replacement, wherein the core wire comprises a medical grade stainless steel alloy and the diameter D_(core) of the core wire in at least the distal end portion provides a flexural modulus of 60 GPa or more.
 12. The multisensor guidewire of claim 1, configured for measuring a transvalvular blood pressure gradient within the heart during a minimally invasive cardiac intervention, wherein said plurality of optical sensors comprise Fabry-Pérot MOMS pressure sensors and said sensor locations are spaced apart lengthwise along said length of the distal end portion to provide for one or more of: a) placement of at least one pressure sensor in the aorta downstream of the aortic valve and placement of at least one pressure sensor in the left ventricle, upstream of the aortic valve for measurement of a transvalvular blood pressure gradient for the aortic valve; b) placement of at least one pressure sensor in the left atrium upstream of the mitral valve and placement of at least one pressure sensor in the left ventricle, downstream of the mitral valve for measurement of a transvalvular blood pressure gradient for the mitral valve; c) placement of at least one pressure sensor in the right atrium upstream of the tricuspid valve and placement of at least one pressure sensor in the right ventricle, downstream of the tricuspid valve, for measurement of a transvalvular blood pressure gradient for the tricuspid valve; and d) placement of at least one pressure sensor in the right ventricle upstream of the pulmonary valve and placement of at least one pressure sensor in the pulmonary artery, downstream of the pulmonary valve for measurement of a transvalvular blood pressure gradient for the pulmonary valve.
 13. The multisensor guidewire claim 1, wherein the plurality of optical sensors further comprises an optical flow sensor.
 14. The multisensor guidewire of claim 1, for use as a support guidewire for transcatheter valve replacement, comprising at least three optical sensors and respective optical fibers, wherein the distal end portion of the coil has an external diameter ≦0.89 mm (≦0.035 inch), and the core wire provides a guidewire having a flexural modulus of 60 GPa or more.
 15. The multisensor guidewire of claim 1, wherein apertures are provided in the coil adjacent each optical pressure sensor for fluid contact therewith, and optionally, radiopaque markers are provided adjacent each optical pressure sensor.
 16. The multisensor guidewire of claim 1, wherein the guidewire comprises separable distal and proximal parts, and further comprising a separable micro-optical coupler comprising a female connector and a male connector coupling the proximal and distal parts, the distal part carrying the male connector, and the male connector having a diameter no greater than the outside diameter of the coil, to enable proximal mounting of components on/over-the-guidewire.
 17. The multisensor guidewire of claim 1, wherein the plurality of optical sensors further comprises an optical contact force sensor adjacent to, or within, the distal tip, the optical contact force sensor being configured for sensing a force applied by the distal end portion of the guidewire to surrounding tissue.
 18. The multisensor guidewire of claim 1, wherein the flexible distal tip comprises a pre-formed atraumatic tip comprising one of: a straight soft tip; a pre-formed J-tip, a pre-formed spiral tip or other two dimensionally curved tip; a pre-formed tip having a three dimensional curved form; a pre-formed tip having a helical structure; and a pre-formed tip having a tapered helical structure, resembling the form of a snail shell.
 19. A core wire for a multisensor guidewire as defined in claim 1, wherein the multisensor guidewire has a flexible coil having an external diameter of ≦1 mm and comprises a plurality of optical sensors and a corresponding plurality of optical fibers, the core wire being formed from a medical grade metal alloy, having a diameter D_(core) and an external surface defining a plurality of grooves extending along the length of the guidewire, each groove having a depth that can accommodate an individual one of said plurality of optical fibers within the diameter D_(core) of the core wire, and wherein D_(core) is sized to fit slideably with the flexible coil of a guidewire.
 20. The core wire of claim 19, wherein the plurality of grooves extend helically along the length of the core wire.
 21. The core wire of claim 19, wherein the plurality of grooves are spaced symmetrically around the core wire.
 22. The core wire of claim 19, wherein surfaces of the grooves have at least a minimum radius for formation of the grooves by wire-drawing.
 23. The core wire of claim 19, fabricated from a stainless steel alloy.
 24. A method of assembly of a multisensor guidewire as defined in claim 1, the method comprising: providing a core wire having an external surface and cross-sectional profile defining a plurality of grooves defined along its length; providing a plurality of optical fibers, each optical fiber having at its distal end an optical sensor; attaching the optical fibers and their respective optical sensors and the core wire to form a sub-assembly with optical sensors spaced apart lengthwise along a distal end portion of the core wire, and with each optical fiber and its respective sensor sitting within a respective groove of the core wire; and inserting the sub-assembly into the coil of the guidewire. 